. , Left-right symmetry breaking mediated via asymmetric cell migration and adhesion

S. .. Harlepp, C. Ramspacher, D. Wu, F. Monduc, S. Bhat et al., Molecular and subcellular chirality in the process of left-right patterning, Cell contractility and forces associated with left-right organizer formation, vol.74, pp.4426-4434, 2013.

P. Avasthi and W. F. Marshall, Stages of ciliogenesis and regulation of ciliary length, Differentiation, vol.83, pp.30-42, 2012.

M. Bayraktar and J. Manner, Cardiac looping may be driven by compressive loads resulting from unequal growth of the heart and pericardial cavity. Observations on a physical simulation model, Front. Physiol, vol.5, p.112, 2014.

M. Behrndt, G. Salbreux, P. Campinho, R. Hauschild, F. Oswald et al., Forces driving epithelial spreading in zebrafish gastrulation, Science, vol.338, pp.257-260, 2012.

M. Blum, T. Beyer, T. Weber, P. Vick, P. Andre et al., Xenopus, an ideal model system to study vertebrate left-right asymmetry, Dev. Dyn, vol.238, pp.1215-1225, 2009.

M. Blum, K. Feistel, T. Thumberger, and A. Schweickert, The evolution and conservation of left-right patterning mechanisms, Development, vol.141, pp.1603-1613, 2014.

A. Borovina, S. Superina, D. Voskas, and B. Ciruna, Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia, Nat. Cell Biol, vol.12, pp.407-412, 2010.

F. Boselli, J. B. Freund, and J. Vermot, Blood flow mechanics in cardiovascular development, Cell. Mol. Life Sci, vol.72, pp.2545-2559, 2015.

N. A. Brown and L. Wolpert, The development of handedness in left/right asymmetry, Development, vol.109, pp.1-9, 1990.

R. D. Burdine and A. F. Schier, Conserved and divergent mechanisms in left-right axis formation, Genes Dev, vol.14, pp.763-776, 2000.

D. Caballero, R. Voituriez, and D. Riveline, The cell ratchet: interplay between efficient protrusions and adhesion determines cell motion, Cell Adhes. Migr, vol.9, pp.327-334, 2015.

J. Capdevila, K. J. Vogan, C. J. Tabin, and J. C. Izpisua-belmonte, Mechanisms of left-right determination in vertebrates, Cell, vol.101, pp.9-21, 2000.

J. H. Cartwright, O. Piro, and I. Tuval, Fluid dynamics in developmental biology: moving fluids that shape ontogeny, HFSP J, vol.3, pp.77-93, 2009.

T. H. Chen, J. J. Hsu, X. Zhao, C. Guo, M. N. Wong et al., Left-right symmetry breaking in tissue morphogenesis via cytoskeletal mechanics, Circ. Res, vol.110, pp.551-559, 2012.

Y. H. Chien, R. Keller, C. Kintner, and D. R. Shook, Mechanical strain determines the axis of planar polarity in ciliated epithelia, Curr. Biol, vol.25, pp.2774-2784, 2015.

H. Clevers, Modeling development and disease with organoids, Cell, vol.165, pp.1586-1597, 2016.

J. R. Colantonio, J. Vermot, D. Wu, A. D. Langenbacher, S. Fraser et al., The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear, Nature, vol.457, pp.205-209, 2009.

J. Comelles, D. Caballero, R. Voituriez, V. Hortiguela, V. Wollrab et al., Cells as active particles in asymmetric potentials: motility under external gradients, Biophys. J, vol.107, pp.1513-1522, 2014.
DOI : 10.1016/j.bpj.2014.11.2487

URL : https://doi.org/10.1016/j.bpj.2014.11.2487

J. Compagnon, V. Barone, S. Rajshekar, R. Kottmeier, K. Pranjic-ferscha et al., The notochord breaks bilateral symmetry by controlling cell shapes in the zebrafish laterality organ, Dev. Cell, vol.31, pp.774-783, 2014.

C. Cui, C. D. Little, and B. J. Rongish, Rotation of organizer tissue contributes to left-right asymmetry, Anat. Rec. (Hoboken), vol.292, pp.557-561, 2009.
DOI : 10.1002/ar.20872

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1002/ar.20872

N. M. Davis, N. A. Kurpios, X. Sun, J. Gros, J. F. Martin et al., The chirality of gut rotation derives from left-right asymmetric changes in the architecture of the dorsal mesentery, Dev. Cell, vol.15, pp.134-145, 2008.

R. J. Dekker, S. Van-soest, R. D. Fontijn, S. Salamanca, P. G. De-groot et al., Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2), Blood, vol.100, pp.1689-1698, 2002.

M. Delling, A. A. Indzhykulian, X. Liu, Y. Li, T. Xie et al., Primary cilia are not calcium-responsive mechanosensors, Nature, vol.531, pp.656-660, 2016.
DOI : 10.1038/nature17426

URL : http://europepmc.org/articles/pmc4851444?pdf=render

P. Delmas, S. M. Nauli, X. Li, B. Coste, N. Osorio et al., Gating of the polycystin ion channel signaling complex in neurons and kidney cells, FASEB J, vol.18, pp.740-742, 2004.

J. Du, X. Ma, B. Shen, Y. Huang, L. Birnbaumer et al., TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel, FASEB J, vol.28, pp.4677-4685, 2014.
DOI : 10.1096/fj.14-251652

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200325/pdf

J. J. Essner, J. D. Amack, M. K. Nyholm, E. B. Harris, and H. J. Yost, Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut, Development, vol.132, pp.1247-1260, 2005.

E. Farge, Mechanical induction of twist in the Drosophila foregut/stomodeal primordium, Curr. Biol, vol.13, pp.1365-1377, 2003.

F. Farina, J. Gaillard, C. Guerin, Y. Coute, J. Sillibourne et al., The centrosome is an actin-organizing centre, Nat. Cell Biol, vol.18, p.65, 2016.
DOI : 10.1038/ncb3285

URL : https://hal.archives-ouvertes.fr/hal-01261646

M. E. Fernandez-sanchez, F. Serman, P. Ahmadi, and E. Farge, Mechanical induction in embryonic development and tumor growth integrative cues through molecular to multicellular interplay and evolutionary perspectives, Methods Cell Biol, vol.98, pp.295-321, 2010.
DOI : 10.1016/s0091-679x(10)98012-6

M. E. Fernandez-sanchez, S. Barbier, J. Whitehead, G. Bealle, A. Michel et al., Mechanical induction of the tumorigenic beta-catenin pathway by tumour growth pressure, Nature, vol.523, pp.92-95, 2015.

S. Field, K. L. Riley, D. T. Grimes, H. Hilton, M. Simon et al., Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2, Development, vol.138, pp.1131-1142, 2011.
DOI : 10.1242/dev.058149

URL : http://dev.biologists.org/content/138/6/1131.full.pdf

A. S. Forouhar, M. Liebling, A. Hickerson, A. Nasiraei-moghaddam, H. J. Tsai et al., The embryonic vertebrate heart tube is a dynamic suction pump, Science, vol.312, pp.751-753, 2006.
DOI : 10.1126/science.1123775

URL : https://authors.library.caltech.edu/41227/7/Forouhar.SOM.pdf

J. B. Freund, J. G. Goetz, K. L. Hill, and J. Vermot, Fluid flows and forces in development: functions, features and biophysical principles, Development, vol.139, pp.1229-1245, 2012.
DOI : 10.1242/dev.085902

URL : http://dev.biologists.org/content/139/16/3063.full.pdf

M. I. Garcia-castro, E. Vielmetter, and M. Bronner-fraser, N-cadherin, a cell adhesion molecule involved in establishment of embryonic left-right asymmetry, Science, vol.288, pp.1047-1051, 2000.

C. Geminard, N. Gonzalez-morales, J. B. Coutelis, and S. Noselli, The myosin ID pathway and left-right asymmetry in Drosophila, Genesis, vol.52, pp.471-480, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00968738

A. Giamarchi, F. Padilla, B. Coste, M. Raoux, M. Crest et al., The versatile nature of the calcium-permeable cation channel TRPP2, EMBO Rep, vol.7, pp.787-793, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00091359

J. G. Goetz, E. Steed, R. R. Ferreira, S. Roth, C. Ramspacher et al., Endothelial cilia mediate low flow sensing during zebrafish vascular development, Cell Rep, vol.6, pp.799-808, 2014.
DOI : 10.1016/j.celrep.2014.01.032

URL : https://hal.archives-ouvertes.fr/hal-01311698

N. Gonzalez-morales, C. Geminard, G. Lebreton, D. Cerezo, J. B. Coutelis et al., The atypical cadherin Dachsous controls left-right asymmetry in Drosophila, Dev. Cell, vol.33, pp.675-689, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01254733

S. W. Grill, Growing up is stressful: biophysical laws of morphogenesis, Curr. Opin. Genet. Dev, vol.21, pp.647-652, 2011.
DOI : 10.1016/j.gde.2011.09.005

D. T. Grimes, J. L. Keynton, M. T. Buenavista, X. Jin, S. H. Patel et al., Genetic analysis reveals a hierarchy of interactions between polycystin-encoding genes and genes controlling cilia function during left-right determination, PLoS Genet, vol.12, p.1006070, 2016.

J. Gros, K. Feistel, C. Viebahn, M. Blum, and C. J. Tabin, Cell movements at Hensen's node establish left/right asymmetric gene expression in the chick, Science, vol.324, pp.941-944, 2009.

B. Guirao, A. Meunier, S. Mortaud, A. Aguilar, J. M. Corsi et al., Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia, Nat. Cell Biol, vol.12, pp.341-350, 2010.
DOI : 10.1038/ncb2040

URL : https://hal.archives-ouvertes.fr/hal-00555153

C. Hahn and M. A. Schwartz, Mechanotransduction in vascular physiology and atherogenesis, Nat. Rev. Mol. Cell Biol, vol.10, pp.53-62, 2009.
DOI : 10.1038/nrm2596

URL : http://europepmc.org/articles/pmc2719300?pdf=render

H. Hamada, Role of physical forces in embryonic development, Semin. Cell Dev. Biol, pp.88-91, 2015.

H. Hamada, C. Meno, D. Watanabe, and Y. Saijoh, Establishment of vertebrate leftright asymmetry, Nat. Rev. Genet, vol.3, pp.103-113, 2002.
DOI : 10.1038/nrg732

K. Hanaoka, F. Qian, A. Boletta, A. K. Bhumia, K. Piontek et al., Co-assembly of polycystin-1 and-2 produces unique cation-permeable currents, Nature, vol.408, pp.990-994, 2000.
DOI : 10.1038/35050128

M. Hashimoto and H. Hamada, Translation of anterior-posterior polarity into left-right polarity in the mouse embryo, Curr. Opin. Genet. Dev, vol.20, pp.433-437, 2010.

M. Hashimoto, K. Shinohara, J. Wang, S. Ikeuchi, S. Yoshiba et al., Planar polarization of node cells determines the rotational axis of node cilia, Nat. Cell Biol, vol.12, pp.170-176, 2010.

E. Heckel, F. Boselli, S. Roth, A. Krudewig, H. G. Belting et al., Oscillatory flow modulates mechanosensitive klf2a expression through trpv4 and trpp2 during heart valve development, Curr. Biol, vol.25, pp.1354-1361, 2015.
DOI : 10.1016/j.cub.2015.03.038

URL : https://doi.org/10.1016/j.cub.2015.03.038

C. P. Heisenberg and Y. Bellaiche, Forces in tissue morphogenesis and patterning, Cell, vol.153, pp.948-962, 2013.
DOI : 10.1016/j.cell.2013.05.008

URL : https://doi.org/10.1016/j.cell.2013.05.008

F. Hildebrandt, T. Benzing, and N. Katsanis, Ciliopathies. N. Engl. J. Med, vol.364, pp.1533-1543, 2011.

A. Hilfinger, F. Julicher, R. Hiramatsu, T. Matsuoka, C. Kimura-yoshida et al., External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos, Phys. Biol, vol.5, pp.131-144, 2008.

T. Hochgreb-hagele, C. Yin, D. E. Koo, M. E. Bronner, and D. Y. Stainier, Laminin beta1a controls distinct steps during the establishment of digestive organ laterality, Development, vol.140, pp.2734-2745, 2013.

S. Horne-badovinac, M. Rebagliati, and D. Y. Stainier, A cellular framework for gutlooping morphogenesis in zebrafish, Science, vol.302, pp.662-665, 2003.

J. R. Hove, R. W. Koster, A. S. Forouhar, G. Acevedo-bolton, S. E. Fraser et al., Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis, Nature, vol.421, pp.172-177, 2003.

S. Hozumi, R. Maeda, K. Taniguchi, M. Kanai, S. Shirakabe et al., An unconventional myosin in Drosophila reverses the default handedness in visceral organs, Nature, vol.440, pp.798-802, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00320713

S. Huveneers and J. De-rooij, Mechanosensitive systems at the cadherin-F-actin interface, J. Cell Sci, vol.126, pp.403-413, 2013.
DOI : 10.1242/jcs.109447

URL : http://jcs.biologists.org/content/joces/126/2/403.full.pdf

H. Ishikawa and W. F. Marshall, Mechanobiology of ciliogenesis, Bioscience, vol.64, pp.1084-1091, 2014.
DOI : 10.1093/biosci/biu173

URL : http://europepmc.org/articles/pmc4776693?pdf=render

K. Kamura, D. Kobayashi, Y. Uehara, S. Koshida, N. Iijima et al., Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis, Development, vol.138, pp.1121-1129, 2011.
DOI : 10.1242/dev.058271

URL : http://dev.biologists.org/content/develop/138/6/1121.full.pdf

J. Keeling, L. Tsiokas, and D. Maskey, Cellular mechanisms of ciliary length control, Cell, vol.5, 2016.
DOI : 10.3390/cells5010006

URL : http://www.mdpi.com/2073-4409/5/1/6/pdf

S. Kim, H. Nie, V. Nesin, U. Tran, P. Outeda et al., The polycystin complex mediates Wnt/Ca(2+) signalling, 2016.
DOI : 10.1038/ncb3363

URL : http://europepmc.org/articles/pmc4925210?pdf=render

, Nat. Cell Biol, vol.18, pp.752-764

A. G. Kramer-zucker, F. Olale, C. J. Haycraft, B. K. Yoder, A. F. Schier et al., Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis, Development, vol.132, pp.1907-1921, 2005.

J. A. Kreiling, G. Williams, and R. Creton, Analysis of Kupffer's vesicle in zebrafish embryos using a cave automated virtual environment, Dev. Dyn, vol.236, pp.1963-1969, 2007.

N. A. Kurpios, M. Ibanes, N. M. Davis, W. Lui, T. Katz et al., The direction of gut looping is established by changes in the extracellular matrix and in cell:cell adhesion, Proc. Natl. Acad. Sci. U. S. A, vol.105, pp.8499-8506, 2008.

B. Ladoux, E. Anon, M. Lambert, A. Rabodzey, P. Hersen et al., Strength dependence of cadherin-mediated adhesions, Biophys. J, vol.98, pp.534-542, 2010.

B. Ladoux, R. M. Mege, and X. Trepat, Front-rear polarization by mechanical cues: from single cells to tissues, Trends Cell Biol, vol.26, pp.420-433, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01307708

T. Lecuit and A. S. Yap, E-cadherin junctions as active mechanical integrators in tissue dynamics, Nat. Cell Biol, vol.17, pp.533-539, 2015.

T. Lecuit, P. F. Lenne, and E. Munro, Force generation, transmission, and integration during cell and tissue morphogenesis, Annu. Rev. Cell Dev. Biol, vol.27, pp.157-184, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00726446

J. S. Lee, Q. Yu, J. T. Shin, E. Sebzda, C. Bertozzi et al., Klf2 is an essential regulator of vascular hemodynamic forces in vivo, Dev. Cell, vol.11, pp.845-857, 2006.

L. Legoff and T. Lecuit, Mechanical forces and growth in animal tissues, Cold Spring Harb. Perspect. Biol, vol.8, p.19232, 2016.

M. Levin, Left-right asymmetry in embryonic development: a comprehensive review, Mech. Dev, vol.122, pp.3-25, 2005.

M. Levin and M. Mercola, The compulsion of chirality: toward an understanding of left-right asymmetry, Genes Dev, vol.12, pp.763-769, 1998.

J. Li, B. Hou, S. Tumova, K. Muraki, A. Bruns et al., Piezo1 integration of vascular architecture with physiological force, Nature, vol.515, pp.279-282, 2014.

K. K. Linask, X. Yu, Y. Chen, and M. D. Han, Directionality of heart looping: effects of Pitx2c misexpression on flectin asymmetry and midline structures, Dev. Biol, vol.246, pp.407-417, 2002.

K. K. Linask, M. D. Han, K. L. Linask, T. Schlange, and T. Brand, Effects of antisense misexpression of CFC on downstream flectin protein expression during heart looping, Dev. Dyn, vol.228, pp.217-230, 2003.

W. Lu, S. H. Seeholzer, M. Han, A. S. Arnold, M. Serrano et al., Cellular nonmuscle myosins NMHC-IIA and NMHC-IIB and vertebrate heart looping, Dev. Dyn, vol.237, pp.3577-3590, 2008.
DOI : 10.1002/dvdy.21645

URL : http://onlinelibrary.wiley.com/doi/10.1002/dvdy.21645/pdf

A. Mahadevan, I. C. Welsh, A. Sivakumar, D. W. Gludish, A. R. Shilvock et al., The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine, Dev. Cell, vol.31, pp.690-706, 2014.

J. L. Maitre, H. Berthoumieux, S. F. Krens, G. Salbreux, F. Julicher et al., Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells, Science, vol.338, pp.253-256, 2012.

T. Mammoto and D. E. Ingber, Mechanical control of tissue and organ development, Development, vol.137, pp.1407-1420, 2010.
DOI : 10.1242/dev.024166

URL : http://dev.biologists.org/content/137/9/1407.full.pdf

A. Mammoto, T. Mammoto, and D. E. Ingber, Mechanosensitive mechanisms in transcriptional regulation, J. Cell Sci, vol.125, pp.3061-3073, 2012.
DOI : 10.1242/jcs.093005

URL : http://jcs.biologists.org/content/125/13/3061.full.pdf

G. Mcdowell, S. Rajadurai, and M. Levin, From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left-right patterning, Philos. Trans. R. Soc. Lond. B. Biol. Sci, vol.371, 2016.

J. Mcgrath, S. Somlo, S. Makova, X. Tian, and M. Brueckner, Two populations of node monocilia initiate left-right asymmetry in the mouse, Cell, vol.114, pp.61-73, 2003.

R. V. Mendes, G. G. Martins, A. M. Cristovao, and L. Saude, N-cadherin locks left-right asymmetry by ending the leftward movement of Hensen's node cells, Dev. Cell, vol.30, pp.353-360, 2014.

V. Mirabet, P. Das, A. Boudaoud, and O. Hamant, The role of mechanical forces in plant morphogenesis, Annu. Rev. Plant Biol, vol.62, pp.365-385, 2011.

S. R. Naganathan, S. Furthauer, M. Nishikawa, F. Julicher, S. W. Grill et al., Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking, Curr. Opin. Cell Biol, vol.3, pp.24-30, 2014.
DOI : 10.7554/elife.04165

URL : https://cdn.elifesciences.org/articles/04165/elife-04165-v1.pdf

T. Nakamura, N. Mine, E. Nakaguchi, A. Mochizuki, M. Yamamoto et al., Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system, Dev. Cell, vol.11, pp.495-504, 2006.

S. M. Nauli, F. J. Alenghat, Y. Luo, E. Williams, P. Vassilev et al., Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells, Nat. Genet, vol.33, pp.129-137, 2003.

S. M. Nauli, Y. Kawanabe, J. J. Kaminski, W. J. Pearce, D. E. Ingber et al., Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1, Circulation, vol.117, pp.1161-1171, 2008.
DOI : 10.1161/circulationaha.107.710111

URL : http://circ.ahajournals.org/content/circulationaha/117/9/1161.full.pdf

A. N. Ng, T. A. De-jong-curtain, D. J. Mawdsley, S. J. White, J. Shin et al., Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis, Dev. Biol, vol.286, pp.114-135, 2005.

S. Nicoli, C. Standley, P. Walker, A. Hurlstone, K. E. Fogarty et al., MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis, Nature, vol.464, pp.1196-1200, 2010.
DOI : 10.1038/nature08889

URL : http://europepmc.org/articles/pmc2914488?pdf=render

E. S. Noel, M. Verhoeven, A. K. Lagendijk, F. Tessadori, K. Smith et al., A nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality, Nat. Commun, vol.4, p.2754, 2013.

S. Nonaka, Y. Tanaka, Y. Okada, S. Takeda, A. Harada et al., Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein, Cell, vol.95, pp.829-837, 1998.

E. A. Ober, H. A. Field, and D. Y. Stainier, From endoderm formation to liver and pancreas development in zebrafish, Mech. Dev, vol.120, pp.5-18, 2003.
DOI : 10.1016/s0925-4773(02)00327-1

URL : https://doi.org/10.1016/s0925-4773(02)00327-1

S. Ohata, V. Herranz-perez, J. Nakatani, A. Boletta, J. M. Garcia-verdugo et al., Mechanosensory genes Pkd1 and Pkd2 contribute to the planar polarization of brain ventricular epithelium, J. Neurosci, vol.35, pp.11153-11168, 2015.
DOI : 10.1523/jneurosci.0686-15.2015

URL : http://www.jneurosci.org/content/jneuro/35/31/11153.full.pdf

N. Okabe, B. Xu, and R. D. Burdine, Fluid dynamics in zebrafish Kupffer's vesicle, Dev. Dyn, vol.237, pp.3602-3612, 2008.
DOI : 10.1016/j.ydbio.2008.05.398

URL : https://doi.org/10.1016/j.ydbio.2008.05.398

Y. Okada, S. Takeda, Y. Tanaka, J. C. Izpisua-belmonte, and N. Hirokawa, Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination, Cell, vol.121, pp.633-644, 2005.

T. Okumura, H. Fujiwara, K. Taniguchi, J. Kuroda, N. Nakazawa et al., Left-right asymmetric morphogenesis of the anterior midgut depends on the activation of a non-muscle myosin II in Drosophila, Dev. Biol, vol.344, pp.693-706, 2010.

L. Pardanaud and A. Eichmann, Stem cells: the stress of forming blood cells, Nature, vol.459, pp.1068-1069, 2009.

A. Patel, R. Sharif-naeini, J. R. Folgering, D. Bichet, F. Duprat et al., Canonical TRP channels and mechanotransduction: from physiology to disease states, Pflugers Arch, vol.460, pp.571-581, 2010.
DOI : 10.1007/s00424-010-0847-8

URL : https://hal.archives-ouvertes.fr/hal-00497147

G. J. Pazour, J. T. San-agustin, J. A. Follit, J. L. Rosenbaum, and G. B. Witman, Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease, Curr. Biol, vol.12, pp.378-380, 2002.

P. Pennekamp, C. Karcher, A. Fischer, A. Schweickert, B. Skryabin et al., The ion channel polycystin-2 is required for left-right axis determination in mice, Curr. Biol, vol.12, pp.938-943, 2002.
DOI : 10.1016/s0960-9822(02)00869-2

URL : https://doi.org/10.1016/s0960-9822(02)00869-2

P. Pennekamp, T. Menchen, B. Dworniczak, and H. Hamada, Situs inversus and ciliary abnormalities: 20 years later, 2015.
DOI : 10.1186/s13630-014-0010-9

URL : https://ciliajournal.biomedcentral.com/track/pdf/10.1186/s13630-014-0010-9

M. Peralta, E. Steed, S. Harlepp, J. M. Gonzalez-rosa, F. Monduc et al., Heartbeat-driven pericardiac fluid forces contribute to epicardium morphogenesis, Curr. Biol, vol.23, pp.1726-1735, 2013.
DOI : 10.1016/j.cub.2013.07.005

URL : https://doi.org/10.1016/j.cub.2013.07.005

A. G. Petzoldt, J. B. Coutelis, C. Geminard, P. Speder, M. Suzanne et al., DE-cadherin regulates unconventional myosin ID and myosin IC in Drosophila left-right asymmetry establishment, Development, vol.139, pp.1874-1884, 2012.
DOI : 10.1242/jcs.112862

URL : https://hal.archives-ouvertes.fr/hal-00757467

A. Pitaval, Q. Tseng, M. Bornens, and M. Thery, Cell shape and contractility regulate ciliogenesis in cell cycle-arrested cells, J. Cell Biol, vol.191, pp.303-312, 2010.
DOI : 10.1083/jcb.201004003

URL : http://europepmc.org/articles/pmc2958475?pdf=render

C. Pohl and Z. Bao, Chiral forces organize left-right patterning in C. elegans by uncoupling midline and anteroposterior axis, Dev. Cell, vol.19, pp.402-412, 2010.
DOI : 10.1016/j.devcel.2010.08.014

URL : https://doi.org/10.1016/j.devcel.2010.08.014

O. Pourquie, Vertebrate segmentation: from cyclic gene networks to scoliosis, Cell, vol.145, pp.650-663, 2011.

S. S. Ranade, Z. Qiu, S. H. Woo, S. S. Hur, S. E. Murthy et al., Piezo1, a mechanically activated ion channel, is required for vascular development in mice, Proc. Natl. Acad. Sci. U. S. A, vol.111, pp.10347-10352, 2014.
DOI : 10.1073/pnas.1409233111

URL : http://www.pnas.org/content/111/28/10347.full.pdf

P. Sampaio, R. R. Ferreira, A. Guerrero, P. Pintado, B. Tavares et al., Left-right organizer flow dynamics: how much cilia activity reliably yields laterality?, Dev. Cell, vol.29, pp.716-728, 2014.
DOI : 10.1016/j.devcel.2014.04.030

URL : https://doi.org/10.1016/j.devcel.2014.04.030

T. Savin, N. A. Kurpios, A. E. Shyer, P. Florescu, H. Liang et al., On the growth and form of the gut, Nature, vol.476, pp.57-62, 2011.

K. Sawamoto, H. Wichterle, O. Gonzalez-perez, J. A. Cholfin, M. Yamada et al., New neurons follow the flow of cerebrospinal fluid in the adult brain, Science, vol.311, pp.629-632, 2006.

S. Schonegg, A. A. Hyman, and W. B. Wood, Timing and mechanism of the initial cue establishing handed left-right asymmetry in Caenorhabditis elegans embryos, Genesis, vol.52, pp.572-580, 2014.

J. Schottenfeld, J. Sullivan-brown, and R. D. Burdine, Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw, Development, vol.134, pp.1605-1615, 2007.
DOI : 10.1242/dev.02827

URL : http://dev.biologists.org/content/develop/134/8/1605.full.pdf

A. Schweickert, T. Weber, T. Beyer, P. Vick, S. Bogusch et al., Ciliadriven leftward flow determines laterality in Xenopus, Curr. Biol, vol.17, pp.60-66, 2007.
DOI : 10.1016/j.cub.2006.10.067

URL : https://doi.org/10.1016/j.cub.2006.10.067

A. J. Sehnert, A. Huq, B. M. Weinstein, C. Walker, M. Fishman et al., Cardiac troponin T is essential in sarcomere assembly and cardiac contractility, Nat. Genet, vol.31, pp.106-110, 2002.
DOI : 10.1038/ng875

URL : http://www.nature.com/ng/journal/v31/n1/pdf/ng875.pdf

R. Sharif-naeini, J. H. Folgering, D. Bichet, F. Duprat, I. Lauritzen et al., Polycystin-1 and-2 dosage regulates pressure sensing, Cell, vol.139, pp.587-596, 2009.

R. Sharif-naeini, J. H. Folgering, D. Bichet, F. Duprat, P. Delmas et al., Sensing pressure in the cardiovascular system: Gq-coupled mechanoreceptors and TRP channels, J. Mol. Cell. Cardiol, vol.48, pp.83-89, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00417369

Y. Shi, J. Yao, J. M. Young, J. A. Fee, R. Perucchio et al., Bending and twisting the embryonic heart: a computational model for c-looping based on realistic geometry, Front. Physiol, vol.5, p.622, 2012.

D. Singh and C. Pohl, Coupling of rotational cortical flow, asymmetric midbody positioning, and spindle rotation mediates dorsoventral axis formation in C. elegans, Dev. Cell, vol.28, pp.253-267, 2014.

H. Song, J. Hu, W. Chen, G. Elliott, P. Andre et al., Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning, Nature, vol.466, pp.378-382, 2010.

P. Speder and S. Noselli, Left-right asymmetry: class I myosins show the direction, Curr. Opin. Cell Biol, vol.19, pp.82-87, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00318530

P. Speder, G. Adam, and S. Noselli, Type ID unconventional myosin controls left-right asymmetry in Drosophila, Nature, vol.440, pp.803-807, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00320707

G. F. Striedter, S. Srinivasan, and E. S. Monuki, Cortical folding: when, where, how, and why?, Annu. Rev. Neurosci, vol.38, pp.291-307, 2008.

K. Sugimura, P. F. Lenne, and F. Graner, Measuring forces and stresses in situ in living tissues, Development, vol.143, pp.186-196, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01445876

W. Supatto and J. Vermot, From cilia hydrodynamics to zebrafish embryonic development, Curr. Top. Dev. Biol, vol.95, pp.33-66, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00841220

S. Superina, A. Borovina, and B. Ciruna, Analysis of maternal-zygotic ugdh mutants reveals divergent roles for HSPGs in vertebrate embryogenesis and provides new insight into the initiation of left-right asymmetry, Dev. Biol, vol.387, pp.154-166, 2014.

C. J. Tabin and K. J. Vogan, A two-cilia model for vertebrate left-right axis specification, Genes Dev, vol.17, pp.1-6, 2003.

K. Taniguchi, R. Maeda, T. Ando, T. Okumura, N. Nakazawa et al., Chirality in planar cell shape contributes to left-right asymmetric epithelial morphogenesis, Science, vol.333, pp.339-341, 2011.

Y. H. Tee, T. Shemesh, V. Thiagarajan, R. F. Hariadi, K. L. Anderson et al., Cellular chirality arising from the self-organization of the actin cytoskeleton, Nat. Cell Biol, vol.17, pp.445-457, 2015.

D. A. Turner, C. R. Glodowski, A. C. Luz, P. Baillie-johnson, P. C. Hayward et al., Interactions between Nodal and Wnt signalling Drive Robust Symmetry Breaking and Axial Organisation in Gastruloids (Embryonic Organoids), 2016.

L. Vincensini, T. Blisnick, and P. Bastin, 1001 model organisms to study cilia and flagella, Biol. Cell, vol.103, pp.109-130, 2011.

V. Vogel and M. Sheetz, Local force and geometry sensing regulate cell functions, Nat. Rev. Mol. Cell Biol, vol.7, pp.265-275, 2006.

D. A. Voronov, P. W. Alford, G. Xu, and L. A. Taber, The role of mechanical forces in dextral rotation during cardiac looping in the chick embryo, Dev. Biol, vol.272, pp.339-350, 2004.

K. N. Wallace and M. Pack, Unique and conserved aspects of gut development in zebrafish, Dev. Biol, vol.255, pp.12-29, 2003.

G. Wang, A. B. Cadwallader, D. S. Jang, M. Tsang, H. J. Yost et al., The Rho kinase Rock2b establishes anteroposterior asymmetry of the ciliated Kupffer's vesicle in zebrafish, Development, vol.138, pp.45-54, 2011.

G. Wang, M. L. Manning, and J. D. Amack, Regional cell shape changes control form and function of Kupffer's vesicle in the zebrafish embryo, Dev. Biol, vol.370, pp.52-62, 2012.

G. F. Weber, M. A. Bjerke, and D. W. Desimone, A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration, Dev. Cell, vol.22, pp.104-115, 2012.
DOI : 10.1016/j.devcel.2011.10.013

URL : https://doi.org/10.1016/j.devcel.2011.10.013

L. Wei, K. Imanaka-yoshida, L. Wang, S. Zhan, M. D. Schneider et al., Inhibition of Rho family GTPases by Rho GDP dissociation inhibitor disrupts cardiac morphogenesis and inhibits cardiomyocyte proliferation, Development, vol.129, pp.1705-1714, 2002.

I. C. Welsh, M. Thomsen, D. W. Gludish, C. Alfonso-parra, Y. Bai et al., Integration of left-right Pitx2 transcription and Wnt signaling drives asymmetric gut morphogenesis via Daam2, Dev. Cell, vol.26, pp.629-644, 2013.
DOI : 10.1016/j.devcel.2013.07.019

URL : https://doi.org/10.1016/j.devcel.2013.07.019

J. P. White, M. Cibelli, L. Urban, B. Nilius, J. G. Mcgeown et al., TRPV4: molecular conductor of a diverse orchestra, Physiol. Rev, vol.96, pp.911-973, 2016.
DOI : 10.1152/physrev.00016.2015

URL : http://physrev.physiology.org/content/physrev/96/3/911.full.pdf

D. Wu, J. B. Freund, S. E. Fraser, and J. Vermot, Mechanistic basis of otolith formation during teleost inner ear development, Dev. Cell, vol.20, pp.271-278, 2011.
DOI : 10.1016/j.devcel.2010.12.006

URL : https://doi.org/10.1016/j.devcel.2010.12.006

K. Yashiro, H. Shiratori, and H. Hamada, Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch, Nature, vol.450, pp.285-288, 2007.

C. Yin, K. Kikuchi, T. Hochgreb, K. D. Poss, and D. Y. Stainier, Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish, Dev. Cell, vol.18, pp.973-984, 2010.
DOI : 10.1016/j.devcel.2010.05.009

URL : https://doi.org/10.1016/j.devcel.2010.05.009

B. K. Yoder, X. Hou, and L. M. Guay-woodford, The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia, J. Am. Soc. Nephrol, vol.13, pp.2508-2516, 2002.
DOI : 10.1097/01.asn.0000029587.47950.25

URL : http://jasn.asnjournals.org/content/13/10/2508.full.pdf

S. Yoshiba, H. Shiratori, I. Y. Kuo, A. Kawasumi, K. Shinohara et al., Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2, Science, vol.338, pp.226-231, 2012.

S. Yuan, L. Zhao, M. Brueckner, and Z. Sun, Intraciliary calcium oscillations initiate vertebrate left-right asymmetry, Curr. Biol, vol.25, pp.556-567, 2015.
DOI : 10.1016/j.cub.2014.12.051

URL : https://doi.org/10.1016/j.cub.2014.12.051

H. Zhang and M. Labouesse, Signalling through mechanical inputs: a coordinated process, J. Cell Sci, vol.125, pp.3039-3049, 2012.
DOI : 10.1242/jcs.119776

URL : http://jcs.biologists.org/content/125/17/4172.full.pdf

H. Zhang, C. Gally, and M. Labouesse, Tissue morphogenesis: how multiple cells cooperate to generate a tissue, Curr. Opin. Cell Biol, vol.22, pp.575-582, 2010.
DOI : 10.1016/j.ceb.2010.08.011

A. Borovina, S. Superina, D. Voskas, C. , and B. , Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia, Nat Cell Biol, vol.12, pp.407-412, 2010.

W. Supatto and J. Vermot, From cilia hydrodynamics to zebrafish embryonic development, Curr Top Dev Biol, vol.95, pp.33-66, 2011.
DOI : 10.1016/b978-0-12-385065-2.00002-5

URL : https://hal.archives-ouvertes.fr/hal-00841220

D. Beis, T. Bartman, S. W. Jin, I. C. Scott, L. A. Amico et al., Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development, Development, vol.132, pp.4193-4204, 2005.
DOI : 10.1242/dev.01970

URL : http://dev.biologists.org/content/develop/132/18/4193.full.pdf

A. Borovina, S. Superina, D. Voskas, C. , and B. , Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia, Nat Cell Biol, vol.12, pp.407-412, 2010.

C. Boucher and R. Sandford, Autosomal dominant polycystic kidney disease (ADPKD, MIM 173900, PKD1 and PKD2 genes, protein products known as polycystin-1 and polycystin-2), Eur J Hum Genet, vol.12, pp.347-354, 2004.
DOI : 10.1038/sj.ejhg.5201162

URL : http://www.nature.com/ejhg/journal/v12/n5/pdf/5201162a.pdf

J. R. Colantonio, J. Vermot, D. Wu, A. D. Langenbacher, S. Fraser et al., The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear, Nature, vol.457, pp.205-209, 2009.

M. Delling, A. A. Indzhykulian, X. Liu, Y. Li, T. Xie et al., Primary cilia are not calciumresponsive mechanosensors, Nature, vol.531, pp.656-660, 2016.
DOI : 10.1038/nature17426

URL : http://europepmc.org/articles/pmc4851444?pdf=render

J. J. Essner, J. D. Amack, M. K. Nyholm, E. B. Harris, and H. J. Yost, Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut, Development, vol.132, pp.1247-1260, 2005.

J. J. Essner, K. J. Vogan, M. K. Wagner, C. J. Tabin, H. J. Yost et al., Conserved function for embryonic nodal cilia, Nature, vol.418, pp.37-38, 2002.

R. R. Ferreira and J. Vermot, The balancing roles of mechanical forces during left-right patterning and asymmetric morphogenesis, Mech Dev, 2016.

S. Field, K. L. Riley, D. T. Grimes, H. Hilton, M. Simon et al., Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2, Development, vol.138, pp.1131-1142, 2011.

M. Fliegauf, T. Benzing, and H. Omran, When cilia go bad: cilia defects and ciliopathies, Nat Rev Mol Cell Biol, vol.8, pp.880-893, 2007.

L. Francescatto, S. C. Rothschild, A. L. Myers, and R. M. Tombes, The activation of membrane targeted CaMK-II in the zebrafish Kupffer's vesicle is required for left-right asymmetry, Development, vol.137, pp.2753-2762, 2010.

S. Gonzalez-perrett, K. Kim, C. Ibarra, A. E. Damiano, E. Zotta et al., Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+permeable nonselective cation channel, Proc Natl Acad Sci U S A, vol.98, pp.1182-1187, 2001.

B. Guirao, A. Meunier, S. Mortaud, A. Aguilar, J. M. Corsi et al., Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia, Nat Cell Biol, vol.12, pp.341-350, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00555153

H. Hamada, C. Meno, D. Watanabe, and Y. Saijoh, Establishment of vertebrate left-right asymmetry, Nat Rev Genet, vol.3, pp.103-113, 2002.

K. Hanaoka, F. Qian, A. Boletta, A. K. Bhunia, K. Piontek et al., Co-assembly of polycystin-1 and-2 produces unique cation-permeable currents, Nature, vol.408, pp.990-994, 2000.

M. Hashimoto, K. Shinohara, J. Wang, S. Ikeuchi, S. Yoshiba et al., Planar polarization of node cells determines the rotational axis of node cilia, Nat Cell Biol, vol.12, pp.170-176, 2010.

C. P. Heisenberg and C. Volhard, The function of silberblick in the positioning of the eye anlage in the zebrafish embryo, Dev Biol, vol.184, pp.85-94, 1997.

C. P. Heisenberg, M. Tada, G. J. Rauch, L. Saude, M. L. Concha et al., Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation, Nature, vol.405, pp.76-81, 2000.

N. Hirokawa, Y. Tanaka, and Y. Okada, Cilia, KIF3 molecular motor and nodal flow, Curr Opin Cell Biol, vol.24, pp.31-39, 2012.

M. Hojo, S. Takashima, D. Kobayashi, A. Sumeragi, A. Shimada et al., Right-elevated expression of charon is regulated by fluid flow in medaka Kupffer's vesicle, Dev Growth Differ, vol.49, pp.395-405, 2007.

H. Hong, J. Kim, K. , and J. , Myosin heavy chain 10 (MYH10) is required for centriole migration during the biogenesis of primary cilia, Biochem Biophys Res Commun, vol.461, pp.180-185, 2015.

K. M. Jaffe, D. T. Grimes, J. Schottenfeld-roames, M. E. Werner, T. S. Ku et al., c21orf59/kurly Controls Both Cilia Motility and Polarization, vol.14, pp.1841-1849, 2016.
DOI : 10.1016/j.celrep.2016.01.069

URL : https://doi.org/10.1016/j.celrep.2016.01.069

J. R. Jessen and L. Solnica-krezel, Identification and developmental expression pattern of van gogh-like 1, a second zebrafish strabismus homologue, Gene Expr Patterns, vol.4, pp.339-344, 2004.

S. Kalogirou, N. Malissovas, E. Moro, F. Argenton, D. Y. Stainier et al., Intracardiac flow dynamics regulate atrioventricular valve morphogenesis, Cardiovasc Res, vol.104, pp.49-60, 2014.

K. Kamura, D. Kobayashi, Y. Uehara, S. Koshida, N. Iijima et al., Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis, Development, vol.138, pp.1121-1129, 2011.

Y. Kawakami, A. Raya, R. M. Raya, C. Rodriguez-esteban, and J. C. Belmonte, Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo, Results Chapter, vol.435, pp.165-171, 2005.

, Origins of meridional tilt in the left-right organizer

R. N. Kettleborough, E. M. Busch-nentwich, S. A. Harvey, C. M. Dooley, E. De-bruijn et al., A systematic genome-wide analysis of zebrafish protein-coding gene function, Nature, vol.496, pp.494-497, 2013.

B. Kilian, H. Mansukoski, F. C. Barbosa, F. Ulrich, M. Tada et al., The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation, Mech Dev, vol.120, pp.467-476, 2003.

A. G. Kramer-zucker, F. Olale, C. J. Haycraft, B. K. Yoder, A. F. Schier et al., Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis, Development, vol.132, pp.1907-1921, 2005.

J. A. Kreiling, . Prabhat, G. Williams, C. , and R. , Analysis of Kupffer's vesicle in zebrafish embryos using a cave automated virtual environment, Dev Dyn, vol.236, pp.1963-1969, 2007.

C. B. Lindemann and K. A. Lesich, Flagellar and ciliary beating: the proven and the possible, J Cell Sci, vol.123, pp.519-528, 2010.

S. Long, N. Ahmad, R. , and M. , The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry, Development, vol.130, pp.2303-2316, 2003.

S. S. Lopes, R. Lourenco, L. Pacheco, N. Moreno, J. Kreiling et al., Notch signalling regulates left-right asymmetry through ciliary length control, Development, vol.137, pp.3625-3632, 2010.
DOI : 10.1242/dev.054452

URL : http://dev.biologists.org/content/137/21/3625.full.pdf

F. Marlow, F. Zwartkruis, J. Malicki, S. C. Neuhauss, L. Abbas et al., Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish, Dev Biol, vol.203, pp.382-399, 1998.

W. F. Marshall and C. Kintner, Cilia orientation and the fluid mechanics of development, Curr Opin Cell Biol, vol.20, pp.48-52, 2008.

J. Mcgrath, S. Somlo, S. Makova, X. Tian, and M. Brueckner, Two populations of node monocilia initiate left-right asymmetry in the mouse, Cell, vol.114, pp.61-73, 2003.

R. Monteiro, M. Van-dinther, J. Bakkers, R. Wilkinson, R. Patient et al., Two novel type II receptors mediate BMP signalling and are required to establish left-right asymmetry in zebrafish, Dev Biol, vol.315, pp.55-71, 2008.

T. D. Montenegro-johnson, D. I. Baker, D. J. Smith, and S. S. Lopes, Three-dimensional flow in Kupffer's Vesicle, J Math Biol, 2016.

T. Nakamura and H. Hamada, Left-right patterning: conserved and divergent mechanisms, Development, vol.139, pp.3257-3262, 2012.
DOI : 10.1242/dev.061606

URL : http://dev.biologists.org/content/139/18/3257.full.pdf

S. Nonaka, S. Yoshiba, D. Watanabe, S. Ikeuchi, T. Goto et al., De novo formation of leftright asymmetry by posterior tilt of nodal cilia, PLoS Biol, vol.3, p.268, 2005.

N. Okabe, B. Xu, and R. D. Burdine, Fluid dynamics in zebrafish Kupffer's vesicle, Dev Dyn, vol.237, pp.3602-3612, 2008.

Y. Okada, S. Takeda, Y. Tanaka, J. C. Izpisua-belmonte, and N. Hirokawa, Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination, Cell, vol.121, pp.633-644, 2005.

P. Pennekamp, C. Karcher, A. Fischer, A. Schweickert, B. Skryabin et al., The ion channel polycystin-2 is required for left-right axis determination in mice, Curr Biol, vol.12, pp.938-943, 2002.

A. Pitaval, Q. Tseng, M. Bornens, and M. Thery, Cell shape and contractility regulate ciliogenesis in cell cycle-arrested cells, J Cell Biol, vol.191, pp.303-312, 2010.

A. F. Ramsdell, Left-right asymmetry and congenital cardiac defects: getting to the heart of the matter in vertebrate leftright axis determination, Dev Biol, vol.288, pp.1-20, 2005.

P. Sampaio, R. R. Ferreira, A. Guerrero, P. Pintado, B. Tavares et al., Left-right organizer flow dynamics: how much cilia activity reliably yields laterality, vol.29, pp.716-728, 2014.

B. Sarmah, A. J. Latimer, B. Appel, and S. R. Wente, Inositol polyphosphates regulate zebrafish left-right asymmetry, Dev Cell, vol.9, pp.133-145, 2005.
DOI : 10.1016/j.devcel.2005.05.002

URL : https://doi.org/10.1016/j.devcel.2005.05.002

J. Schottenfeld, J. Sullivan-brown, and R. D. Burdine, Zebrafish curly up encodes a Pkd2 ortholog that restricts leftside-specific expression of southpaw, Development, vol.134, pp.1605-1615, 2007.

A. Schweickert, T. Weber, T. Beyer, P. Vick, S. Bogusch et al., Cilia-driven leftward flow determines laterality in Xenopus, Curr Biol, vol.17, pp.60-66, 2007.

A. J. Shapiro, S. D. Davis, T. Ferkol, S. D. Dell, M. Rosenfeld et al., Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy, Chest, vol.146, pp.1176-1186, 2014.

J. Sullivan-brown, J. Schottenfeld, N. Okabe, C. L. Hostetter, F. C. Serluca et al., , 2008.

, Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants, Dev Biol, vol.314, pp.261-275

W. Supatto, S. E. Fraser, and J. Vermot, An all-optical approach for probing microscopic flows in living embryos, 2008.

, Biophys J, vol.95, pp.29-31

W. Supatto and J. Vermot, From cilia hydrodynamics to zebrafish embryonic development, Curr Top Dev Biol, vol.95, pp.33-66, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00841220

M. J. Sutherland, W. , and S. M. , Disorders of left-right asymmetry: heterotaxy and situs inversus, Am J Med Genet C Semin Med Genet, vol.151, pp.307-317, 2009.

, Origins of meridional tilt in the left-right organizer

C. Thisse, T. , and B. , High-resolution in situ hybridization to whole-mount zebrafish embryos, Nat Protoc, vol.3, pp.59-69, 2008.

P. M. Vassilev, L. Guo, X. Z. Chen, Y. Segal, J. B. Peng et al., Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease, Biochem Biophys Res Commun, vol.282, pp.341-350, 2001.

G. Wang, A. B. Cadwallader, D. S. Jang, M. Tsang, H. J. Yost et al., The Rho kinase Rock2b establishes anteroposterior asymmetry of the ciliated Kupffer's vesicle in zebrafish, Development, vol.138, pp.45-54, 2011.

G. Wang, M. L. Manning, and J. D. Amack, Regional cell shape changes control form and function of Kupffer's vesicle in the zebrafish embryo, Dev Biol, vol.370, pp.52-62, 2012.

M. Wu, Y. , and S. , New Insights into the Molecular Mechanisms Targeting Tubular Channels/Transporters in PKD Development, Kidney Dis (Basel), vol.2, pp.128-135, 2016.

S. Yoshiba, H. Shiratori, I. Y. Kuo, A. Kawasumi, K. Shinohara et al., Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2, Science, vol.338, pp.226-231, 2012.

S. Yuan, L. Zhao, M. Brueckner, Z. ;. Sun, K. R. Robinson et al., Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates, References References Adams, vol.25, pp.1657-1671, 2006.

B. A. Afzelius, A human syndrome caused by immotile cilia, Science, vol.193, pp.317-319, 1976.
DOI : 10.1126/science.1084576

A. Alqadah, Y. W. Hsieh, C. , and C. F. , microRNA function in left-right neuronal asymmetry: perspectives from C. elegans, Front Cell Neurosci, vol.7, p.158, 2013.
DOI : 10.3389/fncel.2013.00158

URL : https://www.frontiersin.org/articles/10.3389/fncel.2013.00158/pdf

J. D. Amack, Salient features of the ciliated organ of asymmetry, Bioarchitecture, vol.4, pp.6-15, 2014.

J. D. Amack, X. Wang, and H. J. Yost, Two T-box genes play independent and cooperative roles to regulate morphogenesis of ciliated Kupffer's vesicle in zebrafish, Dev Biol, vol.310, pp.196-210, 2007.

D. Antic, J. L. Stubbs, K. Suyama, C. Kintner, M. P. Scott et al., Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis, PLoS One, vol.5, p.8999, 2010.
DOI : 10.1371/journal.pone.0008999

URL : https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008999&type=printable

H. Anton, S. Harlepp, C. Ramspacher, D. Wu, F. Monduc et al., Pulse propagation by a capacitive mechanism drives embryonic blood flow, Development, vol.140, pp.4426-4434, 2013.
DOI : 10.1242/dev.096768

URL : http://dev.biologists.org/content/develop/140/21/4426.full.pdf

J. L. Badano, N. Mitsuma, P. L. Beales, and N. Katsanis, The ciliopathies: an emerging class of human genetic disorders, Annu Rev Genomics Hum Genet, vol.7, pp.125-148, 2006.

B. Bajoghli, N. Aghaallaei, D. Soroldoni, C. , and T. , The roles of Groucho/Tle in left-right asymmetry and Kupffer's vesicle organogenesis, Dev Biol, vol.303, pp.347-361, 2007.

C. Battle, C. M. Ott, D. T. Burnette, J. Lippincott-schwartz, and C. F. Schmidt, Intracellular and extracellular forces drive primary cilia movement, Proc Natl Acad Sci U S A, vol.112, pp.1410-1415, 2015.
DOI : 10.1073/pnas.1421845112

URL : http://www.pnas.org/content/112/5/1410.full.pdf

D. Beis, T. Bartman, S. W. Jin, I. C. Scott, L. A. Amico et al., Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development, Development, vol.132, p.4193, 2005.
DOI : 10.1242/dev.01970

URL : http://dev.biologists.org/content/develop/132/18/4193.full.pdf

E. Bell, I. Munoz-sanjuan, C. R. Altmann, A. Vonica, and A. H. Brivanlou, Cell fate specification and competence by, 2003.

. Coco, T. Bmp, and W. Inhibitor, Development, vol.130, pp.1381-1389

J. A. Belo, A. C. Silva, A. C. Borges, M. Filipe, M. Bento et al., Generating asymmetries in the early vertebrate embryo: the role of the Cerberus-like family, Int J Dev Biol, vol.53, pp.1399-1407, 2009.

N. F. Berbari, A. K. O'connor, C. J. Haycraft, and B. K. Yoder, The primary cilium as a complex signaling center, Curr Biol, vol.19, pp.526-535, 2009.

P. Berens, CircStat: A MATLAB Toolbox for Circular Statistics, Journal of Statistical Software, vol.31, 2009.

B. W. Bisgrove and H. J. Yost, The roles of cilia in developmental disorders and disease, Development, vol.133, pp.4131-4143, 2006.

R. A. Bloodgood, Sensory reception is an attribute of both primary cilia and motile cilia, J Cell Sci, vol.123, pp.505-509, 2010.

M. Blum, P. Andre, K. Muders, A. Schweickert, A. Fischer et al., Ciliation and gene expression distinguish between node and posterior notochord in the mammalian embryo, Xenopus, an ideal model system to study vertebrate left-right asymmetry, vol.75, pp.1215-1225, 2007.

M. Blum, K. Feistel, T. Thumberger, and A. Schweickert, The evolution and conservation of left-right patterning mechanisms, Development, vol.141, pp.1603-1613, 2014.

M. Blum, A. Schweickert, P. Vick, C. V. Wright, and M. V. Danilchik, Symmetry breakage in the vertebrate embryo: when does it happen and how does it work?, Dev Biol, vol.393, pp.109-123, 2014.

T. Boettger, L. Wittler, and M. Kessel, FGF8 functions in the specification of the right body side of the chick, Curr Biol, vol.9, pp.277-280, 1999.

M. Bornens, The centrosome in cells and organisms, Science, vol.335, pp.422-426, 2012.

A. Borovina, S. Superina, D. Voskas, C. , and B. , Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia, Nat Cell Biol, vol.12, pp.407-412, 2010.

C. Boucher and R. Sandford, Autosomal dominant polycystic kidney disease (ADPKD, MIM 173900, p.2, 2004.

, protein products known as polycystin-1 and polycystin-2), Eur J Hum Genet, vol.12, pp.347-354

N. A. Brown and L. Wolpert, The development of handedness in left/right asymmetry, Development, vol.109, pp.1-9, 1990.

M. Brueckner, Heterotaxia, congenital heart disease, and primary ciliary dyskinesia, Circulation, vol.115, pp.2793-2795, 2007.
DOI : 10.1161/circulationaha.107.699256

URL : https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.107.699256

A. R. Brummett and J. N. Dumont, Kupffer's vesicle in Fundulus heteroclitus: a scanning and transmission electron microscope study, Tissue Cell, vol.10, pp.11-22, 1978.

J. Capdevila, K. J. Vogan, C. J. Tabin, and J. C. Belmonte, Mechanisms of left-right determination in vertebrates, Cell, vol.101, pp.9-21, 2000.

J. H. Cartwright, N. Piro, O. Piro, and I. Tuval, Embryonic nodal flow and the dynamics of nodal vesicular parcels, J R Soc Interface, vol.4, pp.49-55, 2007.

J. H. Cartwright, N. Piro, O. Piro, and I. Tuval, Fluid dynamics of nodal flow and left-right patterning in development, 2008.

, Dev Dyn, vol.237, pp.3477-3490

J. H. Cartwright, O. Piro, and I. Tuval, Fluid-dynamical basis of the embryonic development of left-right asymmetry in vertebrates, Proc Natl Acad Sci U S A, vol.101, pp.7234-7239, 2004.

J. H. Cartwright, O. Piro, and I. Tuval, Fluid dynamics in developmental biology: moving fluids that shape ontogeny, 2009.

, HFSP J, vol.3, pp.77-93

T. Caspary, C. E. Larkins, A. , and K. V. , The graded response to Sonic Hedgehog depends on cilia architecture, 2007.

, Dev Cell, vol.12, pp.767-778

V. H. Castleman, L. Romio, R. Chodhari, R. A. Hirst, S. C. De-castro et al., Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities, Am J Hum Genet, vol.84, pp.197-209, 2009.

C. A. Clement, K. D. Ajbro, K. Koefoed, M. L. Vestergaard, I. R. Veland et al., TGF-beta signaling is associated with endocytosis at the pocket region of the primary cilium, Cell Rep, vol.3, pp.1806-1814, 2013.

E. Cocucci, G. Racchetti, and J. Meldolesi, Shedding microvesicles: artefacts no more, Trends Cell Biol, vol.19, pp.43-51, 2009.

J. R. Colantonio, J. Vermot, D. Wu, A. D. Langenbacher, S. Fraser et al., The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear, Nature, vol.457, pp.205-209, 2009.

J. Collignon, I. Varlet, and E. J. Robertson, Relationship between asymmetric nodal expression and the direction of embryonic turning, Nature, vol.381, pp.155-158, 1996.
DOI : 10.1038/381155a0

J. Compagnon, V. Barone, S. Rajshekar, R. Kottmeier, K. Pranjic-ferscha et al., The notochord breaks bilateral symmetry by controlling cell shapes in the zebrafish laterality organ, Dev Cell, vol.31, pp.774-783, 2014.

M. S. Cooper and L. A. Amico, A cluster of noninvoluting endocytic cells at the margin of the zebrafish blastoderm marks the site of embryonic shield formation, Dev Biol, vol.180, pp.184-198, 1996.

J. B. Coutelis, N. Gonzalez-morales, C. Geminard, and S. Noselli, Diversity and convergence in the mechanisms establishing L/R asymmetry in metazoa, EMBO Rep, vol.15, pp.926-937, 2014.

C. Cui, C. D. Little, and B. J. Rongish, Rotation of organizer tissue contributes to left-right asymmetry, Anat Rec (Hoboken), vol.292, pp.557-561, 2009.
DOI : 10.1002/ar.20872

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1002/ar.20872

A. Dasgupta and J. D. Amack, Cilia in vertebrate left-right patterning, Philos Trans R Soc Lond B Biol Sci, p.371, 2016.
DOI : 10.1098/rstb.2015.0410

URL : http://rstb.royalsocietypublishing.org/content/371/1710/20150410.full.pdf

M. Delling, A. A. Indzhykulian, X. Liu, Y. Li, T. Xie et al., Primary cilia are not calciumresponsive mechanosensors, Nature, vol.531, pp.656-660, 2016.
DOI : 10.1038/nature17426

URL : http://europepmc.org/articles/pmc4851444?pdf=render

C. E. Erter, L. Solnica-krezel, W. , and C. V. , Zebrafish nodal-related 2 encodes an early mesendodermal inducer signaling from the extraembryonic yolk syncytial layer, Dev Biol, vol.204, pp.361-372, 1998.
DOI : 10.1006/dbio.1998.9097

URL : https://doi.org/10.1006/dbio.1998.9097

J. J. Essner, J. D. Amack, M. K. Nyholm, E. B. Harris, and H. J. Yost, Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut, Development, vol.132, pp.1247-1260, 2005.

J. J. Essner, K. J. Vogan, M. K. Wagner, C. J. Tabin, H. J. Yost et al., Conserved function for embryonic nodal cilia, Nature, vol.418, pp.37-38, 2002.
DOI : 10.1038/418037a

F. Farina, J. Gaillard, C. Guerin, Y. Coute, J. Sillibourne et al., The centrosome is an actinorganizing centre, Nature Cell Biology, vol.18, p.65, 2016.
DOI : 10.1038/ncb3285

URL : https://hal.archives-ouvertes.fr/hal-01261646

B. Feldman, M. A. Gates, E. S. Egan, S. T. Dougan, G. Rennebeck et al., , 1998.

, Zebrafish organizer development and germ-layer formation require nodal-related signals, Nature, vol.395, pp.181-185

M. I. Ferrante, L. Romio, S. Castro, J. E. Collins, D. A. Goulding et al., , 2009.

, Convergent extension movements and ciliary function are mediated by ofd1, a zebrafish orthologue of the human oral-facialdigital type 1 syndrome gene, Hum Mol Genet, vol.18, pp.289-303

R. R. Ferreira and J. Vermot, The balancing roles of mechanical forces during left-right patterning and asymmetric morphogenesis, Mech Dev, vol.144, pp.71-80, 2017.

S. Field, K. L. Riley, D. T. Grimes, H. Hilton, M. Simon et al., Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2, Development, vol.138, pp.1131-1142, 2011.

M. Fliegauf, T. Benzing, H. Omran, L. References-francescatto, S. C. Rothschild et al., The activation of membrane targeted CaMK-II in the zebrafish Kupffer's vesicle is required for left-right asymmetry, Nat Rev Mol Cell Biol, vol.8, pp.2753-2762, 2007.

J. B. Freund, J. G. Goetz, K. L. Hill, and J. Vermot, Fluid flows and forces in development: functions, features and biophysical principles, Development, vol.139, pp.1229-1245, 2012.

T. Fukumoto, I. P. Kema, L. , and M. , Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos, Curr Biol, vol.15, pp.794-803, 2005.

R. H. Giles, H. Ajzenberg, J. , and P. K. , 3D spheroid model of mIMCD3 cells for studying ciliopathies and renal epithelial disorders, Nat Protoc, vol.9, pp.2725-2731, 2014.
DOI : 10.1038/nprot.2014.181

J. G. Goetz, E. Steed, R. R. Ferreira, S. Roth, C. Ramspacher et al., Endothelial cilia mediate low flow sensing during zebrafish vascular development, Cell Rep, vol.6, pp.799-808, 2014.
DOI : 10.1016/j.celrep.2014.01.032

URL : https://hal.archives-ouvertes.fr/hal-01311698

S. C. Goetz, A. , and K. V. , The primary cilium: a signalling centre during vertebrate development, Nat Rev Genet, vol.11, pp.331-344, 2010.
DOI : 10.1038/nrg2774

URL : http://europepmc.org/articles/pmc3121168?pdf=render

J. J. Gokey, Y. Ji, H. G. Tay, B. Litts, and J. D. Amack, Kupffer's vesicle size threshold for robust left-right patterning of the zebrafish embryo, Dev Dyn, vol.245, pp.22-33, 2016.

S. Gomez-lopez, R. G. Lerner, P. , and C. , Asymmetric cell division of stem and progenitor cells during homeostasis and cancer, Cell Mol Life Sci, vol.71, pp.575-597, 2014.

S. Gonzalez-perrett, K. Kim, C. Ibarra, A. E. Damiano, E. Zotta et al., Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+permeable nonselective cation channel, Proc Natl Acad Sci U S A, vol.98, pp.1182-1187, 2001.

J. Gros, K. Feistel, C. Viebahn, M. Blum, and C. J. Tabin, Cell movements at Hensen's node establish left/right asymmetric gene expression in the chick, Science, vol.324, pp.941-944, 2009.
DOI : 10.1126/science.1172478

URL : http://europepmc.org/articles/pmc2993078?pdf=render

B. Guirao, A. Meunier, S. Mortaud, A. Aguilar, J. M. Corsi et al., Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia, Nat Cell Biol, vol.12, pp.341-350, 2010.
DOI : 10.1038/ncb2040

URL : https://hal.archives-ouvertes.fr/hal-00555153

H. Hamada, Breakthroughs and future challenges in left-right patterning, Dev Growth Differ, vol.50, pp.71-78, 2008.
DOI : 10.1111/j.1440-169x.2008.01008.x

H. Hamada, C. Meno, D. Watanabe, and Y. Saijoh, Establishment of vertebrate left-right asymmetry, Nat Rev Genet, vol.3, pp.103-113, 2002.
DOI : 10.1038/nrg732

H. Hamada, T. , and P. P. , Mechanisms of left-right asymmetry and patterning: driver, mediator and responder, 2014.
DOI : 10.12703/p6-110

URL : https://f1000.com/prime/reports/b/6/110/pdf

, F1000Prime Rep 6, p.110

K. Hanaoka, F. Qian, A. Boletta, A. K. Bhunia, K. Piontek et al., Co-assembly of polycystin-1 and-2 produces unique cation-permeable currents, Nature, vol.408, pp.990-994, 2000.

H. Hashimoto, M. Rebagliati, N. Ahmad, O. Muraoka, T. Kurokawa et al., The Cerberus/Dan-family protein Charon is a negative regulator of Nodal signaling during left-right patterning in zebrafish, Development, vol.131, pp.1741-1753, 2004.

M. Hashimoto, K. Shinohara, J. Wang, S. Ikeuchi, S. Yoshiba et al.,

A. , The function of silberblick in the positioning of the eye anlage in the zebrafish embryo, References Heisenberg, vol.12, pp.85-94, 1997.

C. P. Heisenberg, M. Tada, G. J. Rauch, L. Saude, M. L. Concha et al., Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation, Nature, vol.405, pp.76-81, 2000.

N. E. Hellman, Y. Liu, E. Merkel, C. Austin, S. Le-corre et al., The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch, Proc Natl Acad Sci U S A, vol.107, pp.18499-18504, 2010.

F. Hildebrandt, T. Benzing, and N. Katsanis, Ciliopathies. N Engl J Med, vol.364, pp.1533-1543, 2011.

A. Hilfinger, J. , and F. , The chirality of ciliary beats, Phys Biol, vol.5, p.16003, 2008.
DOI : 10.1088/1478-3975/5/1/016003

N. Hirokawa, Y. Tanaka, and Y. Okada, Left-right determination: involvement of molecular motor KIF3, cilia, and nodal flow, Cold Spring Harb Perspect Biol, vol.1, p.802, 2009.
DOI : 10.1101/cshperspect.a000802

URL : http://cshperspectives.cshlp.org/content/1/1/a000802.full.pdf

N. Hirokawa, Y. Tanaka, and Y. Okada, Cilia, KIF3 molecular motor and nodal flow, Curr Opin Cell Biol, vol.24, pp.31-39, 2012.
DOI : 10.1016/j.ceb.2012.01.002

N. Hirokawa, Y. Tanaka, Y. Okada, and S. Takeda, Nodal flow and the generation of left-right asymmetry, Cell, vol.125, pp.33-45, 2006.

M. C. Hogan, L. Manganelli, J. R. Woollard, A. I. Masyuk, T. V. Masyuk et al., Characterization of PKD protein-positive exosome-like vesicles, J Am Soc Nephrol, vol.20, pp.278-288, 2009.
DOI : 10.1681/asn.2008060564

URL : http://jasn.asnjournals.org/content/20/2/278.full.pdf

M. Hojo, S. Takashima, D. Kobayashi, A. Sumeragi, A. Shimada et al., Right-elevated expression of charon is regulated by fluid flow in medaka Kupffer's vesicle, Dev Growth Differ, vol.49, p.395, 2007.

H. Hong, J. Kim, K. , and J. , Myosin heavy chain 10 (MYH10) is required for centriole migration during the biogenesis of primary cilia, Biochem Biophys Res Commun, vol.461, pp.180-185, 2015.

J. R. Hove, R. W. Koster, A. S. Forouhar, G. Acevedo-bolton, S. E. Fraser et al., Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis, Nature, vol.421, pp.172-177, 2003.
DOI : 10.1038/nature01282

J. M. Inacio, S. Marques, T. Nakamura, K. Shinohara, C. Meno et al., The dynamic right-to-left translocation of Cerl2 is involved in the regulation and termination of Nodal activity in the mouse node, PLoS One, vol.8, p.60406, 2013.

M. Inaki, J. Liu, and K. Matsuno, Cell chirality: its origin and roles in left-right asymmetric development, Philos Trans R Soc Lond B Biol Sci, p.371, 2016.
DOI : 10.1098/rstb.2015.0403

URL : http://rstb.royalsocietypublishing.org/content/371/1710/20150403.full.pdf

M. Inoue, M. Tanimoto, O. , and Y. , The role of ear stone size in hair cell acoustic sensory transduction, Sci Rep, vol.3, 2013.

H. Ishikawa, M. , and W. F. , Ciliogenesis: building the cell's antenna, Nat Rev Mol Cell Biol, vol.12, pp.222-234, 2011.
DOI : 10.1038/nrm3085

K. M. Jaffe, D. T. Grimes, J. Schottenfeld-roames, M. E. Werner, T. S. Ku et al., c21orf59/kurly Controls Both Cilia Motility and Polarization, vol.14, pp.1841-1849, 2016.
DOI : 10.1016/j.celrep.2016.01.069

URL : https://doi.org/10.1016/j.celrep.2016.01.069

J. R. Jessen and L. Solnica-krezel, Identification and developmental expression pattern of van gogh-like 1, a second zebrafish strabismus homologue, Gene Expr Patterns, vol.4, pp.339-344, 2004.
DOI : 10.1016/j.modgep.2003.09.012

C. M. Jones, M. R. Kuehn, B. L. Hogan, J. C. Smith, W. et al., Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation, Development, vol.121, pp.3651-3662, 1995.

E. M. Joseph and D. A. Melton, Xnr4: a Xenopus nodal-related gene expressed in the Spemann organizer, Dev Biol, vol.184, pp.367-372, 1997.
DOI : 10.1006/dbio.1997.8510

URL : https://doi.org/10.1006/dbio.1997.8510

S. Kalogirou, N. Malissovas, E. Moro, F. Argenton, D. Y. Stainier et al., Intracardiac flow dynamics regulate atrioventricular valve morphogenesis, Cardiovasc Res, vol.104, pp.49-60, 2014.
DOI : 10.1093/cvr/cvu186

URL : https://academic.oup.com/cardiovascres/article-pdf/104/1/49/17195724/cvu186.pdf

K. Kamura, D. Kobayashi, Y. Uehara, S. Koshida, N. Iijima et al., Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis, Development, vol.138, pp.1121-1129, 2011.
DOI : 10.1242/dev.058271

URL : http://dev.biologists.org/content/develop/138/6/1121.full.pdf

M. Kartagener, Zur Pathogenese der Bronchiektasien. I. Mitteilung Bronchiektasien bei Situs viscerum inversus, Beitr Klin Tuberk Spezif Tuberkuloseforsch, pp.498-501, 1933.
DOI : 10.1007/bf02141633

Y. Kawakami, A. Raya, R. M. Raya, C. Rodriguez-esteban, and J. C. Belmonte, Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo, Nature, vol.435, pp.165-171, 2005.
DOI : 10.1038/nature03512

A. Kawasumi, T. Nakamura, N. Iwai, K. Yashiro, Y. Saijoh et al., , 2011.

, Dev Biol, vol.353, pp.321-330

R. N. Kettleborough, E. M. Busch-nentwich, S. A. Harvey, C. M. Dooley, E. De-bruijn et al., A systematic genome-wide analysis of zebrafish protein-coding gene function, Nature, vol.496, pp.494-497, 2013.

B. Kilian, H. Mansukoski, F. C. Barbosa, F. Ulrich, M. Tada et al., The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation, Mech Dev, vol.120, pp.467-476, 2003.

C. B. Kimmel, W. W. Ballard, S. R. Kimmel, B. Ullmann, and T. F. Schilling, Stages of embryonic development of the zebrafish, Dev Dyn, vol.203, pp.253-310, 1995.

S. M. King, Axonemal Dynein Arms, Cold Spring Harb Perspect Biol, vol.8, 2016.

S. Konishi, S. Gotoh, K. Tateishi, Y. Yamamoto, Y. Korogi et al., Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells, Stem Cell Reports, vol.6, pp.18-25, 2016.

A. G. Kramer-zucker, F. Olale, C. J. Haycraft, B. K. Yoder, A. F. Schier et al., Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis, Development, vol.132, pp.1907-1921, 2005.

J. A. Kreiling, . Prabhat, G. Williams, C. , and R. , Analysis of Kupffer's vesicle in zebrafish embryos using a cave automated virtual environment, Dev Dyn, vol.236, pp.1963-1969, 2007.

J. D. Lee, A. , and K. V. , Morphogenesis of the node and notochord: the cellular basis for the establishment and maintenance of left-right asymmetry in the mouse, Dev Dyn, vol.237, pp.3464-3476, 2008.

P. Leong, C. , and S. , Methods for spherical data analysis and visualization, J Neurosci Methods, vol.80, pp.191-200, 1998.

M. Levin, Left-right asymmetry in embryonic development: a comprehensive review, Mech Dev, vol.122, pp.3-25, 2005.

M. Levin, R. L. Johnson, C. D. Stern, M. Kuehn, and C. Tabin, A molecular pathway determining left-right asymmetry in chick embryogenesis, Cell, vol.82, pp.803-814, 1995.

M. Levin and M. Mercola, The compulsion of chirality: toward an understanding of left-right asymmetry, Genes Dev, vol.12, pp.763-769, 1998.

M. Levin and M. Mercola, Gap junctions are involved in the early generation of left-right asymmetry, Dev Biol, vol.203, p.90, 1998.

M. Levin and M. Mercola, Gap junction-mediated transfer of left-right patterning signals in the early chick blastoderm is upstream of Shh asymmetry in the node, Development, vol.126, pp.4703-4714, 1999.

M. Levin, S. Pagan, D. J. Roberts, J. Cooke, M. R. Kuehn et al., Left/right patterning signals and the independent regulation of different aspects of situs in the chick embryo, Dev Biol, vol.189, pp.57-67, 1997.

M. Levin, T. Thorlin, K. R. Robinson, T. Nogi, and M. Mercola, Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning, Cell, vol.111, pp.77-89, 2002.

Y. Li, N. T. Klena, G. C. Gabriel, X. Liu, A. J. Kim et al., Global genetic analysis in mice unveils central role for cilia in congenital heart disease, Nature, vol.521, pp.520-524, 2015.

Y. Li, H. Yagi, E. O. Onuoha, R. R. Damerla, R. Francis et al., DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia, PLoS Genet, vol.12, 2016.

C. B. Lindemann and K. A. Lesich, Flagellar and ciliary beating: the proven and the possible, J Cell Sci, vol.123, pp.519-528, 2010.

H. Lodish, B. A. Zipursky, S. L. Matsudaira, P. , B. D. et al., Molecular Cell Biology, 2000.

M. Logan, H. G. Simon, and C. Tabin, Differential regulation of T-box and homeobox transcription factors suggests roles in controlling chick limb-type identity, Development, vol.125, pp.2825-2835, 1998.

S. Long, N. Ahmad, R. , and M. , The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry, Development, vol.130, pp.2303-2316, 2003.

S. S. Lopes, R. Lourenco, L. Pacheco, N. Moreno, J. Kreiling et al., Notch signalling regulates left-right asymmetry through ciliary length control, Development, vol.137, pp.3625-3632, 2010.

R. Lourenço, .. S. , and L. , Symmetry OUT, Asymmetry IN. Symmetry, vol.2, pp.1033-1054, 2010.

L. A. Lowe, D. M. Supp, K. Sampath, T. Yokoyama, C. V. Wright et al., , 1996.

, Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus, Nature, vol.381, pp.158-161

H. Ma, Y. Lin, Z. A. Zhao, X. Lu, Y. Yu et al., MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2, J Biol Chem, vol.291, pp.12126-12135, 2016.

J. J. Malicki, J. , and C. A. , The Cilium: Cellular Antenna and Central Processing Unit, Trends Cell Biol, vol.27, pp.126-140, 2017.

J. Manner, Does an equivalent of the "ventral node" exist in chick embryos? A scanning electron microscopic study, 2001.

, Anat Embryol (Berl), vol.203, pp.481-490

L. Marjoram, W. , and C. , Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus, Development, vol.138, pp.475-485, 2011.

F. Marlow, F. Zwartkruis, J. Malicki, S. C. Neuhauss, L. Abbas et al., , 1998.

, Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish, Dev Biol, vol.203, pp.382-399

S. Marques, A. C. Borges, A. C. Silva, S. Freitas, M. Cordenonsi et al., The activity of the Nodal antagonist, 2004.

, Cerl-2 in the mouse node is required for correct L/R body axis, Genes Dev, vol.18, pp.2342-2347

W. F. Marshall and C. Kintner, Cilia orientation and the fluid mechanics of development, Curr Opin Cell Biol, vol.20, pp.48-52, 2008.

T. Matusek, F. Wendler, S. Poles, S. Pizette, G. Angelo et al., The ESCRT machinery regulates the secretion and long-range activity of Hedgehog, Nature, vol.516, pp.99-103, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01117493

C. Maul, K. , and S. , Image systems for a Stokeslet inside a rigid spherical container, Physics of Fluids, vol.6, pp.2221-2223, 1994.

J. Mcgrath and M. Brueckner, Cilia are at the heart of vertebrate left-right asymmetry, Curr Opin Genet Dev, vol.13, p.385, 2003.

J. Mcgrath, S. Somlo, S. Makova, X. Tian, and M. Brueckner, Two populations of node monocilia initiate left-right asymmetry in the mouse, Cell, vol.114, pp.61-73, 2003.

A. E. Melby, R. M. Warga, and C. B. Kimmel, Specification of cell fates at the dorsal margin of the zebrafish gastrula, Development, vol.122, pp.2225-2237, 1996.

R. V. Mendes, G. G. Martins, A. M. Cristovao, and L. Saude, N-cadherin locks left-right asymmetry by ending the leftward movement of Hensen's node cells, Dev Cell, vol.30, pp.353-360, 2014.

C. Meno, A. Shimono, Y. Saijoh, K. Yashiro, K. Mochida et al., lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal, Cell, vol.94, pp.287-297, 1998.

M. Mercola, Left-right asymmetry: nodal points, J Cell Sci, vol.116, pp.3251-3257, 2003.

M. Mercola, L. , and M. , Left-right asymmetry determination in vertebrates, Annu Rev Cell Dev Biol, vol.17, pp.779-805, 2001.

H. M. Mitchison and E. M. Valente, Motile and non-motile cilia in human pathology: from function to phenotypes, J Pathol, vol.241, pp.294-309, 2017.

R. Monteiro, M. Van-dinther, J. Bakkers, R. Wilkinson, R. Patient et al., Two novel type II receptors mediate BMP signalling and are required to establish left-right asymmetry in zebrafish, Dev Biol, vol.315, pp.55-71, 2008.

T. D. Montenegro-johnson, D. I. Baker, D. J. Smith, and S. S. Lopes, Three-dimensional flow in Kupffer's Vesicle, J Math Biol, 2016.

S. M. Morrow, A. J. Bissette, and S. P. Fletcher, Transmission of chirality through space and across length scales, Nat Nanotechnol, vol.12, pp.410-419, 2017.

M. Muller, K. Heeck, and C. P. Elemans, Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells, PLoS One, vol.11, 2016.

S. R. Naganathan, S. Furthauer, M. Nishikawa, F. Julicher, and S. W. Grill, , 2014.

S. R. Naganathan, T. C. Middelkoop, S. Furthauer, S. W. Grill, J. S. Goldstein et al., An Actin Network Dispatches Ciliary GPCRs into Extracellular Vesicles to Modulate Signaling, Curr Opin Cell Biol, vol.38, pp.252-263, 2016.

T. Nakamura and H. Hamada, Left-right patterning: conserved and divergent mechanisms, Development, vol.139, p.3257, 2012.

T. Nakamura, N. Mine, E. Nakaguchi, A. Mochizuki, M. Yamamoto et al., , 2006.

, Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system, Dev Cell, vol.11, pp.495-504

T. Nakamura, D. Saito, A. Kawasumi, K. Shinohara, Y. Asai et al., Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA, Nat Commun, vol.3, p.1322, 2012.

S. M. Nauli, F. J. Alenghat, Y. Luo, E. Williams, P. Vassilev et al., , 2003.

, Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells, Nat Genet, vol.33, pp.129-137

S. M. Nauli, Y. Kawanabe, J. J. Kaminski, W. J. Pearce, D. E. Ingber et al., Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1, Circulation, vol.117, pp.1161-1171, 2008.
DOI : 10.1161/circulationaha.107.710111

URL : https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.107.710111

S. Nonaka, H. Shiratori, Y. Saijoh, and H. Hamada, Determination of left-right patterning of the mouse embryo by artificial nodal flow, Nature, vol.418, pp.96-99, 2002.

S. Nonaka, Y. Tanaka, Y. Okada, S. Takeda, A. Harada et al., Randomization of leftright asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein, Cell, vol.95, pp.829-837, 1998.

S. Nonaka, S. Yoshiba, D. Watanabe, S. Ikeuchi, T. Goto et al., De novo formation of leftright asymmetry by posterior tilt of nodal cilia, PLoS Biol, vol.3, p.268, 2005.

D. P. Norris, Cilia, calcium and the basis of left-right asymmetry, BMC Biol, vol.10, p.102, 2012.

T. Odate, S. Takeda, K. Narita, and T. Kawahara, 9 + 0 and 9 + 2 cilia are randomly dispersed in the mouse node, 2016.
DOI : 10.1093/jmicro/dfv352

, Microscopy (Oxf), vol.65, pp.119-126

N. Okabe, B. Xu, and R. D. Burdine, Fluid dynamics in zebrafish Kupffer's vesicle, Dev Dyn, vol.237, pp.3602-3612, 2008.
DOI : 10.1016/j.ydbio.2008.05.398

URL : https://doi.org/10.1016/j.ydbio.2008.05.398

Y. Okada, S. Nonaka, Y. Tanaka, Y. Saijoh, H. Hamada et al., Abnormal nodal flow precedes situs inversus in iv and inv mice, Mol Cell, vol.4, pp.459-468, 1999.
DOI : 10.1016/s1097-2765(00)80197-5

URL : https://doi.org/10.1016/s1097-2765(00)80197-5

Y. Okada, S. Takeda, Y. Tanaka, J. C. Izpisua-belmonte, and N. Hirokawa, Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination, Cell, vol.121, pp.633-644, 2005.

P. Oteiza, M. Koppen, M. L. Concha, and C. P. Heisenberg, Origin and shaping of the laterality organ in zebrafish, Development, vol.135, pp.2807-2813, 2008.

S. M. Pagan-westphal and C. J. Tabin, The transfer of left-right positional information during chick embryogenesis, Cell, vol.93, pp.25-35, 1998.

T. J. Park, B. J. Mitchell, P. B. Abitua, C. Kintner, and J. B. Wallingford, Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells, Nat Genet, vol.40, pp.871-879, 2008.

H. Peeters, K. ;. Devriendt, C. Karcher, A. Fischer, A. Schweickert et al., The ion channel polycystin-2 is required for left-right axis determination in mice, References Pennekamp, vol.49, pp.938-943, 2002.

P. Pennekamp, T. Menchen, B. Dworniczak, and H. Hamada, Situs inversus and ciliary abnormalities: 20 years later, 2015.
DOI : 10.1186/s13630-014-0010-9

URL : https://ciliajournal.biomedcentral.com/track/pdf/10.1186/s13630-014-0010-9

S. C. Phua, S. Chiba, M. Suzuki, E. Su, E. C. Roberson et al., Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision, Cell, vol.168, pp.264-279, 2017.

A. Pitaval, Q. Tseng, M. Bornens, and M. Thery, Cell shape and contractility regulate ciliogenesis in cell cycle-arrested cells, J Cell Biol, vol.191, pp.303-312, 2010.
DOI : 10.1083/jcb.201004003

URL : http://jcb.rupress.org/content/191/2/303.full.pdf

O. Pourquie, Vertebrate segmentation: from cyclic gene networks to scoliosis, Cell, vol.145, pp.650-663, 2011.

E. M. Purcell, Life at low Reynolds number, Am J Phys, vol.45, pp.3-11, 1977.
DOI : 10.1063/1.30370

A. F. Ramsdell, Left-right asymmetry and congenital cardiac defects: getting to the heart of the matter in vertebrate leftright axis determination, Dev Biol, vol.288, pp.1-20, 2005.

G. Raposo and W. Stoorvogel, Extracellular vesicles: exosomes, microvesicles, and friends, J Cell Biol, vol.200, pp.373-383, 2013.

A. Raya and J. C. Belmonte, Sequential transfer of left-right information during vertebrate embryo development, Curr Opin Genet Dev, vol.14, pp.575-581, 2004.

A. Raya and J. C. Belmonte, Unveiling the establishment of left-right asymmetry in the chick embryo, Mech Dev, vol.121, pp.1043-1054, 2004.

M. R. Rebagliati, R. Toyama, C. Fricke, P. Haffter, and I. B. Dawid, Zebrafish nodal-related genes are implicated in axial patterning and establishing left-right asymmetry, Dev Biol, vol.199, pp.261-272, 1998.

M. R. Rebagliati, R. Toyama, P. Haffter, and I. B. Dawid, cyclops encodes a nodal-related factor involved in midline signaling, Proc Natl Acad Sci U S A, vol.95, pp.9932-9937, 1998.

A. K. Ryan, B. Blumberg, C. Rodriguez-esteban, S. Yonei-tamura, K. Tamura et al.,

J. Greenwald and S. Choe, Pitx2 determines left-right asymmetry of internal organs in vertebrates, Nature, vol.394, pp.545-551, 1998.

S. Rydholm, G. Zwartz, J. M. Kowalewski, P. Kamali-zare, T. Frisk et al., Mechanical properties of primary cilia regulate the response to fluid flow, Am J Physiol Renal Physiol, vol.298, pp.1096-1102, 2010.

P. Sampaio, R. R. Ferreira, A. Guerrero, P. Pintado, B. Tavares et al., Left-right organizer flow dynamics: how much cilia activity reliably yields laterality, vol.29, pp.716-728, 2014.

K. Sampath, A. L. Rubinstein, A. M. Cheng, J. O. Liang, K. Fekany et al., Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling, Nature, vol.395, pp.185-189, 1998.

B. Sarmah, A. J. Latimer, B. Appel, and S. R. Wente, Inositol polyphosphates regulate zebrafish left-right asymmetry, 2005.

, Dev Cell, vol.9, pp.133-145

B. Sarmah and S. R. Wente, Zebrafish inositol polyphosphate kinases: new effectors of cilia and developmental signaling, Adv Enzyme Regul, vol.50, pp.309-323, 2010.

P. Satir, Chirality of the cytoskeleton in the origins of cellular asymmetry, Philos Trans R Soc Lond B Biol Sci, p.371, 2016.

P. Satir and S. T. Christensen, Overview of structure and function of mammalian cilia, Annu Rev Physiol, vol.69, pp.377-400, 2007.

A. F. Schier, Nodal morphogens, Cold Spring Harb Perspect Biol, vol.1, p.3459, 2009.

J. Schottenfeld, J. Sullivan-brown, and R. D. Burdine, Zebrafish curly up encodes a Pkd2 ortholog that restricts leftside-specific expression of southpaw, Development, vol.134, pp.1605-1615, 2007.

C. M. Schreiner, W. J. Scott, . Jr, D. M. Supp, and S. S. Potter, Correlation of forelimb malformation asymmetries with visceral organ situs in the transgenic mouse insertional mutation, legless, Dev Biol, vol.158, pp.560-562, 1993.

G. C. Schwabe, K. Hoffmann, N. T. Loges, D. Birker, C. Rossier et al., Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations, 2008.

, Hum Mutat, vol.29, pp.289-298

A. Schweickert, P. Vick, M. Getwan, T. Weber, I. Schneider et al., The nodal inhibitor Coco is a critical target of leftward flow in Xenopus, Curr Biol, vol.20, pp.738-743, 2010.

A. Schweickert, T. Weber, T. Beyer, P. Vick, S. Bogusch et al., Cilia-driven leftward flow determines laterality in Xenopus, Curr Biol, vol.17, pp.60-66, 2007.

A. S. Shah, Y. Ben-shahar, T. O. Moninger, J. N. Kline, W. et al., Motile cilia of human airway epithelia are chemosensory, Science, vol.325, pp.1131-1134, 2009.

A. J. Shapiro, S. D. Davis, T. Ferkol, S. D. Dell, M. Rosenfeld et al., Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy, Chest, vol.146, pp.1176-1186, 2014.

M. M. Shen, Nodal signaling: developmental roles and regulation, Development, vol.134, pp.1023-1034, 2007.

K. Shinohara, D. Chen, T. Nishida, K. Misaki, S. Yonemura et al., Absence of Radial Spokes in Mouse Node Cilia Is Required for Rotational Movement but Confers Ultrastructural Instability as a Trade-Off, Dev Cell, vol.35, pp.236-246, 2015.

K. Shinohara and H. Hamada, Cilia in Left-Right Symmetry Breaking, 2017.

K. Shinohara, A. Kawasumi, A. Takamatsu, S. Yoshiba, Y. Botilde et al., Two rotating cilia in the node cavity are sufficient to break left-right symmetry in the mouse embryo, Nat Commun, vol.3, p.622, 2012.

H. Shiratori and H. Hamada, The left-right axis in the mouse: from origin to morphology, Development, vol.133, pp.2095-2104, 2006.

G. Singh, D. M. Supp, C. Schreiner, J. Mcneish, H. J. Merker et al., legless insertional mutation: morphological, molecular, and genetic characterization, Genes Dev, vol.5, pp.2245-2255, 1991.

V. Singla and J. F. Reiter, The primary cilium as the cell's antenna: signaling at a sensory organelle, Science, vol.313, p.629, 2006.

R. D. Sloboda, Intraflagellar transport and the flagellar tip complex, J Cell Biochem, vol.94, pp.266-272, 2005.

D. J. Smith, J. R. Blake, E. A. Gaffney, D. J. Smith, E. A. Gaffney et al., Discrete cilia modelling with singularity distributions: application to the embryonic node and the airway surface liquid, J R Soc Interface, vol.5, pp.1477-1510, 2007.

D. J. Smith, T. D. Montenegro-johnson, and S. S. Lopes, Organized chaos in Kupffer's vesicle: how a heterogeneous structure achieves consistent left-right patterning, Bioarchitecture, vol.4, pp.119-125, 2014.

H. Song, J. Hu, W. Chen, G. Elliott, P. Andre et al., Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning, Nature, vol.466, pp.378-382, 2010.

K. Sulik, D. B. Dehart, T. Iangaki, J. L. Carson, T. Vrablic et al., Morphogenesis of the murine node and notochordal plate, Dev Dyn, vol.201, pp.260-278, 1994.

J. Sullivan-brown, J. Schottenfeld, N. Okabe, C. L. Hostetter, F. C. Serluca et al., , 2008.

, Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants, Dev Biol, vol.314, pp.261-275

C. H. Sung and M. R. Leroux, The roles of evolutionarily conserved functional modules in cilia-related trafficking, Nat Cell Biol, vol.15, pp.1387-1397, 2013.

W. Supatto, S. E. Fraser, and J. Vermot, An all-optical approach for probing microscopic flows in living embryos, 2008.

, Biophys J, vol.95, pp.29-31

W. Supatto and J. Vermot, From cilia hydrodynamics to zebrafish embryonic development, Curr Top Dev Biol, vol.95, p.33, 2011.
DOI : 10.1016/b978-0-12-385065-2.00002-5

URL : https://hal.archives-ouvertes.fr/hal-00841220

D. M. Supp, M. Brueckner, M. R. Kuehn, D. P. Witte, L. A. Lowe et al., Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries, Development, vol.126, pp.5495-5504, 1999.

D. M. Supp, D. P. Witte, S. S. Potter, and M. Brueckner, Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice, Nature, vol.389, pp.963-966, 1997.

M. J. Sutherland, W. , and S. M. , Disorders of left-right asymmetry: heterotaxy and situs inversus, Am J Med Genet C Semin Med Genet, vol.151, pp.307-317, 2009.
DOI : 10.1002/ajmg.c.30228

C. J. Tabin and K. J. Vogan, A two-cilia model for vertebrate left-right axis specification, Genes Dev, vol.17, pp.1-6, 2003.
DOI : 10.1101/gad.1053803

URL : http://genesdev.cshlp.org/content/17/1/1.full.pdf

S. Takahashi, C. Yokota, K. Takano, K. Tanegashima, Y. Onuma et al., Two novel nodalrelated genes initiate early inductive events in Xenopus Nieuwkoop center, Development, vol.127, pp.5319-5329, 2000.

Y. Tanaka, Y. Okada, and N. Hirokawa, FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination, Nature, vol.435, pp.172-177, 2005.

D. Theegarten and M. Ebsen, Ultrastructural pathology of primary ciliary dyskinesia: report about 125 cases in Germany, Diagn Pathol, vol.6, p.115, 2011.

C. Thisse, T. , and B. , High-resolution in situ hybridization to whole-mount zebrafish embryos, Nat Protoc, vol.3, pp.59-69, 2008.
DOI : 10.1038/nprot.2007.514

C. D. Tsiairis and A. P. Mcmahon, An Hh-dependent pathway in lateral plate mesoderm enables the generation of left/right asymmetry, Curr Biol, vol.19, pp.1912-1917, 2009.

N. Tsikolia, S. Schroeder, P. Schwartz, and C. Viebahn, Paraxial left-sided nodal expression and the start of left-right patterning in the early chick embryo, Semin Cell Dev Biol, vol.84, pp.118-133, 2012.

L. N. Vandenberg, J. M. Lemire, L. , and M. , It's never too early to get it Right: A conserved role for the cytoskeleton in left-right asymmetry, Commun Integr Biol, vol.6, 2013.

P. M. Vassilev, L. Guo, X. Z. Chen, Y. Segal, J. B. Peng et al., Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease, Biochem Biophys Res Commun, vol.282, pp.341-350, 2001.

A. Vilfan, Generic flow profiles induced by a beating cilium, Eur Phys J E Soft Matter, vol.35, p.72, 2012.
DOI : 10.1140/epje/i2012-12072-3

A. Vilfan, J. , and F. , Hydrodynamic flow patterns and synchronization of beating cilia, Phys Rev Lett, vol.96, p.58102, 2006.
DOI : 10.1103/physrevlett.96.058102

URL : http://arxiv.org/pdf/physics/0512046

L. Vincensini, T. Blisnick, and P. Bastin, 1001 model organisms to study cilia and flagella, Biol Cell, vol.103, pp.109-130, 2011.
DOI : 10.1042/bc20100104

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1042/BC20100104

A. Vonica and A. H. Brivanlou, The left-right axis is regulated by the interplay of Coco, Xnr1 and derriere in Xenopus embryos, Dev Biol, vol.303, pp.281-294, 2007.

G. H. Wagnière, A. B. Cadwallader, D. S. Jang, M. Tsang, H. J. Yost et al., The Rho kinase Rock2b establishes anteroposterior asymmetry of the ciliated Kupffer's vesicle in zebrafish, On Chirality and the Universal Asymmetry: Reflections on Image and Mirror Image Wang, vol.138, pp.45-54, 2011.

G. Wang, M. L. Manning, and J. D. Amack, Regional cell shape changes control form and function of Kupffer's vesicle in the zebrafish embryo, Dev Biol, vol.370, pp.52-62, 2012.

J. S. Wang, G. Wang, X. Q. Feng, T. Kitamura, Y. L. Kang et al., Hierarchical chirality transfer in the growth of, Towel Gourd tendrils. Sci Rep, vol.3, p.3102, 2013.

X. Wang and H. J. Yost, Initiation and propagation of posterior to anterior (PA) waves in zebrafish left-right development, Dev Dyn, vol.237, pp.3640-3647, 2008.

S. M. Ware, M. G. Aygun, and F. Hildebrandt, Spectrum of clinical diseases caused by disorders of primary cilia, Proc Am Thorac Soc, vol.8, pp.444-450, 2011.

L. Wolpert, Revisiting the F-shaped molecule: is its identity solved?, Genesis, vol.52, pp.455-457, 2014.

C. R. Wood, K. Huang, D. R. Diener, and J. L. Rosenbaum, The cilium secretes bioactive ectosomes, Curr Biol, vol.23, p.906, 2013.

M. Wu, Y. , and S. , New Insights into the Molecular Mechanisms Targeting Tubular Channels/Transporters in PKD Development, Kidney Dis (Basel), vol.2, pp.128-135, 2016.

Y. Yokouchi, K. J. Vogan, R. V. Pearse, and C. J. Tabin, Antagonistic signaling by Caronte, a novel Cerberusrelated gene, establishes left-right asymmetric gene expression, Cell, vol.98, pp.573-583, 1999.

S. Yoshiba and H. Hamada, Roles of cilia, fluid flow, and Ca2+ signaling in breaking of left-right symmetry, Trends Genet, vol.30, pp.10-17, 2014.

S. Yoshiba, H. Shiratori, I. Y. Kuo, A. Kawasumi, K. Shinohara et al., Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2, Nat Genet, vol.338, pp.1445-1453, 2008.

S. Yuan, L. Zhao, M. Brueckner, and Z. Sun, Intraciliary calcium oscillations initiate vertebrate left-right asymmetry, 2015.

, Curr Biol, vol.25, pp.556-567

X. Zhou, H. Sasaki, L. Lowe, B. L. Hogan, M. R. Kuehn et al., Nodal is a novel TGF-beta-like gene expressed in the mouse node during gastrulation, REFERENCES Agullo-Pascual, vol.361, pp.1322-1330, 1993.

J. Anderson, Z. Li, and F. Goubel, Passive stiffness is increased in soleus muscle of desmin knockout mouse, Muscle Nerve, vol.24, pp.1090-1092, 2001.

A. Asimaki, S. Kapoor, E. Plovie, K. Arndt, A. Adams et al., Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy, Sci. Transl. Med, vol.6, pp.40-74, 2014.

J. Balogh, M. Merisckay, Z. Li, D. Paulin, A. et al., Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance, Cardiovasc. Res, vol.53, pp.439-450, 2002.

H. Bä-r, D. Fischer, B. Goudeau, R. A. Kley, C. S. Clemen et al., Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro, Hum. Mol. Genet, vol.14, pp.1251-1260, 2005.

H. Bä-r, N. Mü-cke, A. Kostareva, G. Sjö-berg, U. Aebi et al., Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages, Proc. Natl. Acad. Sci. USA, vol.102, pp.15099-15104, 2005.

H. Bä-r, M. Schopferer, S. Sharma, B. Hochstein, N. Mü-cke et al., Mutations in desmin's carboxy-terminal ''tail'' domain severely modify filament and network mechanics, J. Mol. Biol, vol.397, pp.1188-1198, 2010.

A. Brodehl, P. N. Hedde, M. Dieding, A. Fatima, V. Walhorn et al., Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants, J. Biol. Chem, vol.287, pp.16047-16057, 2012.

, Cell Reports, vol.11, pp.1564-1576, 1575.

N. C. Chi, M. Bussen, K. Brand-arzamendi, C. Ding, J. E. Olgin et al., Cardiac conduction is required to preserve cardiac chamber morphology, Proc. Natl. Acad. Sci. USA, vol.107, pp.14662-14667, 2010.

C. S. Clemen, H. Herrmann, S. V. Strelkov, and R. Schrö-der, Desminopathies: pathology and mechanisms, Acta Neuropathol, vol.125, pp.47-75, 2013.

M. L. Costa, R. Escaleira, A. Cataldo, F. Oliveira, and C. S. Mermelstein, Desmin: molecular interactions and putative functions of the muscle intermediate filament protein, Braz. J. Med. Biol. Res, vol.37, pp.1819-1830, 2004.

D. 'amico, L. Scott, I. C. Jungblut, B. Stainier, and D. Y. , A mutation in zebrafish hmgcr1b reveals a role for isoprenoids in vertebrate heart-tube formation, Curr. Biol, vol.17, pp.252-259, 2007.

A. S. Forouhar, M. Liebling, A. Hickerson, A. Nasiraei-moghaddam, H. J. Tsai et al., The embryonic vertebrate heart tube is a dynamic suction pump, Science, vol.312, pp.751-753, 2006.

J. J. Gard, K. Yamada, K. G. Green, B. C. Eloff, D. S. Rosenbaum et al., Remodeling of gap junctions and slow conduction in a mouse model of desminrelated cardiomyopathy, Cardiovasc. Res, vol.67, pp.539-547, 2005.

L. G. Goldfarb and M. C. Dalakas, Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease, J. Clin. Invest, vol.119, pp.1806-1813, 2009.

R. Griggs, A. Vihola, P. Hackman, K. Talvinen, H. Haravuori et al., Zaspopathy in a large classic late-onset distal myopathy family, Brain, vol.130, pp.1477-1484, 2007.

H. Herrmann, S. V. Strelkov, P. Burkhard, A. , and U. , Intermediate filaments: primary determinants of cell architecture and plasticity, J. Clin. Invest, vol.119, pp.1772-1783, 2009.

L. Herwig, Y. Blum, A. Krudewig, E. Ellertsdottir, A. Lenard et al., Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo, Curr. Biol, vol.21, pp.1942-1948, 2011.

K. Hnia, H. Tronchere, K. K. Tomczak, L. Amoasii, P. Schultz et al., Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle, The Journal of clinical investigation, vol.121, pp.70-85, 2011.

K. Hnia, C. Ramspacher, J. Vermot, and J. Laporte, Desmin in muscle and associated diseases: beyond the structural function, Cell Tissue Res, 2014.

C. J. Huang, C. T. Tu, C. D. Hsiao, F. J. Hsieh, and H. J. Tsai, , 2003.

. Dyn, , vol.228, pp.30-40

J. , P. Chourbagi, O. Hourdé, C. Ferry, A. Butler-browne et al., , 2013.

M. J. Jurynec, R. Xia, J. J. Mackrill, D. Gunther, T. Crawford et al., Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle, Proc. Natl. Acad. Sci. USA, vol.105, pp.12485-12490, 2008.

R. N. Kettleborough, E. M. Busch-nentwich, S. A. Harvey, C. M. Dooley, E. De-bruijn et al., A systematic genome-wide analysis of zebrafish protein-coding gene function, Nature, vol.496, pp.494-497, 2013.

A. Kostareva, G. Sjö-berg, J. Bruton, S. J. Zhang, J. Balogh et al., Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria, J. Muscle Res. Cell Motil, vol.29, pp.25-36, 2008.

P. Lacolley, P. Challande, S. Boumaza, G. Cohuet, S. Laurent et al., Mechanical properties and structure of carotid arteries in mice lacking desmin, Cardiovasc. Res, vol.51, pp.178-187, 2001.

Z. Li, E. Colucci-guyon, M. Pinç-on-raymond, M. Mericskay, S. Pournin et al., Cardiovascular lesions and skeletal myopathy in mice lacking desmin, Dev. Biol, vol.175, pp.362-366, 1996.

M. Li, M. Andersson-lendahl, T. Sejersen, A. , and A. , Knockdown of desmin in zebrafish larvae affects interfilament spacing and mechanical properties of skeletal muscle, J. Gen. Physiol, vol.141, pp.335-345, 2013.

D. J. Milner, G. Weitzer, D. Tran, A. Bradley, C. et al., Disruption of muscle architecture and myocardial degeneration in mice lacking desmin, J. Cell Biol, vol.134, pp.1255-1270, 1996.

H. Mojzisova and J. Vermot, When multiphoton microscopy sees near infrared, Curr. Opin. Genet. Dev, vol.21, pp.549-557, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00667425

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres, Biophys. J, vol.90, pp.693-703, 2006.

J. M. Raats, G. Schaart, J. B. Henderik, A. Van-der-kemp, I. Dunia et al., Muscle-specific expression of a dominant negative desmin mutant in transgenic mice, Eur. J. Cell Biol, vol.71, pp.221-236, 1996.

G. A. Rezniczek, P. Konieczny, B. Nikolic, S. Reipert, D. Schneller et al., Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan, J. Cell Biol, vol.176, pp.965-977, 2007.

B. L. Roman, V. N. Pham, N. D. Lawson, M. Kulik, S. Childs et al., Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels, Development, vol.129, pp.3009-3019, 2002.

R. Schrö-der and B. Schoser, Myofibrillar myopathies: a clinical and myopathological guide, Brain Pathol, vol.19, pp.483-492, 2009.

F. R. Shardonofsky, Y. Capetanaki, and A. M. Boriek, Desmin modulates lung elastic recoil and airway responsiveness, Am. J. Physiol. Lung Cell. Mol. Physiol, vol.290, pp.890-896, 2006.

I. Strate, F. Tessadori, and J. Bakkers, Glypican4 promotes cardiac specification and differentiation by attenuating canonical Wnt and Bmp signaling, Development, vol.142, pp.1767-1776, 2015.

A. Trinh, T. Hochgreb, M. Graham, D. Wu, F. Ruf-zamojski et al., A versatile gene trap to visualize and interrogate the function of the vertebrate proteome, Genes Dev, vol.25, pp.2306-2320, 2011.

K. Y. Van-spaendonck-zwarts, L. Van-hessem, J. D. Jongbloed, H. E. De-walle, Y. Capetanaki et al., Desmin-related myopathy, Clin. Genet, vol.80, pp.354-366, 2011.

B. Vogel, B. Meder, S. Just, C. Laufer, I. Berger et al., In-vivo characterization of human dilated cardiomyopathy genes in zebrafish, Biochem. Biophys. Res. Commun, vol.390, pp.516-522, 2009.

X. Wang, H. Osinska, G. W. Dorn, M. Nieman, J. N. Lorenz et al., Mouse model of desmin-related cardiomyopathy, Circulation, vol.103, pp.2402-2407, 2001.

X. Wang, H. Osinska, R. Klevitsky, A. M. Gerdes, M. Nieman et al., Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice, Circ. Res, vol.89, pp.84-91, 2001.

E. Warp, G. Agarwal, C. Wyart, D. Friedmann, C. S. Oldfield et al., Emergence of patterned activity in the developing zebrafish spinal cord, Curr. Biol, vol.22, pp.93-102, 2012.

H. H. Wu, C. Brennan, and R. Ashworth, Ryanodine receptors, a family of intracellular calcium ion channels, are expressed throughout early vertebrate development, BMC Res. Notes, vol.4, p.541, 2011.

T. Yuri, K. Miki, R. Tsukamoto, A. Shinde, H. Kusaka et al., Autopsy case of desminopathy involving skeletal and cardiac muscle, Pathol. Int, vol.57, pp.32-36, 2007.

H. Zheng, M. Tang, Q. Zheng, A. R. Kumarapeli, K. M. Horak et al., Doxycycline attenuates protein aggregation in cardiomyocytes and improves survival of a mouse model of cardiac proteinopathy, J. Am. Coll. Cardiol, vol.56, pp.1418-1426, 2010.

, The Authors (A) 3D imaging of the heartbeat in Tg(fli:gal4FF; UAS:kaede; cmlc2:egfp) embryos. Heart myocardium is labeled in green (GFP), and endocardium and blood cells are in red, Cell Reports, vol.11, pp.1564-1576, 20152015-06-16.

, The asterisk indicates the absence of a visible endocardial lumen at 24 hpf. The arrows indicate the progressive opening of the lumen at 26 and 30 hpf. (C) 3D sections of the boxed regions in (A). The dashed lines underline the endocardium opening and the arrows show the flow direction. (D) Simplified view of the cardiovascular system of 24-28 hpf embryos

C. V. and ;. Isv, Graphs show the mean and maximum flow velocity in the DA (see box in D) and the pulsatility index (PI) at 24, 26, and 28 hpf. (F) Tracks in the DA are color-coded for their instantaneous velocity over time. (G) 3D anatomy of a 26 hpf heart and its neighboring vasculature and flow direction, See also Movies S5 and S7

H. , Tracks are color-coded for their instantaneous velocity over time. (I) Plots of the velocity and PI observed in a single embryo. Error bars depict SEM

, *p < 0.05, **p < 0.01, ***p < 0.001. See also Figure S1, vol.6, pp.799-808, 20142014-03-13.

, High-speed confocal imaging at 29 fps and digital tracking in a Tg (flk1:mCherry; b-actin:Arl13b-egfp) embryo at 28 hpf. Note the cilium deflection and flow direction (white arrow). See also Movies S13 and S14

, B) Digital tracking permits the segmentation of cilium outlines. Consecutive outlines were color-coded over time during one deflection phase (210 ms)

, C) Cilia deflection angle and flow velocity (see scheme) were quantified overtime and plotted. Note the correlation between maximum and minimum flow velocity and maximum and minimum flow deflection, respectively (red and green arrows)

, D) Cilia deflection in the DA of 24, 26, and 28 hpf embryos. (F) Quantification of (D)

, H and I) Table and graphical display showing the average cilia deflection observed in 28 hpf control and indicated morphant embryos. See also Movie S15, which presents high-speed confocal imaging at 29 fps and digital tracking in a Tg(b-actin:Arl13b-egfp) embryo at 28 hpf injected with the tnnt2a MO. Note the absence of cilium deflection over a 210 ms period and random particle movement (blue track). The cilium is not deflected and remains perpendicular to the vessel wall, G) Calcium content in the developing DA was evaluated and quantified using the endothelial-specific expression of GCAMP3.0 in Tg(fli:gal4FF; UAS: gcamp3.0) embryos. GCAMP3.0 intensity was normalized to the average KAEDE intensity observed in distinct embryos

, K) Calcium content in the developing DA was evaluated in different conditions and quantified using the endothelial-specific expression of GCAMP3

, The diagram shows that the early developing ECs are sensitive to low flow forces. Protruding and highly sensitive primary cilia behave as flow sensors and allow a fine detection of low but increasing flow forces during blood flow onset. Flow-mediated cilia deflection allows a PKD2dependent calcium influx in the endothelium. Error bars depict SEM

, *p < 0.05, **p < 0.01, ***p < 0.001. See also Figures S3 and S4, vol.6, pp.799-808, 20142014-03-13.

W. A. Aboualaiwi, M. Takahashi, B. R. Mell, T. J. Jones, S. Ratnam et al., Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades, Circ. Res, vol.104, pp.860-869, 2009.

B. Shoham, A. Malkinson, G. Krief, S. Shwartz, Y. Ely et al., S1P1 inhibits sprouting angiogenesis during vascular development, Development, vol.139, pp.3859-3869, 2012.
DOI : 10.1242/dev.078550

URL : http://dev.biologists.org/content/139/20/3859.full.pdf

J. Y. Bertrand, N. C. Chi, B. Santoso, S. Teng, D. Y. Stainier et al., Haematopoietic stem cells derive directly from aortic endothelium during development, Nature, vol.464, pp.108-111, 2010.
DOI : 10.1038/nature08738

URL : http://europepmc.org/articles/pmc2858358?pdf=render

A. Borovina, S. Superina, D. Voskas, C. , and B. , Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia, Nat. Cell Biol, vol.12, pp.407-412, 2010.

I. Buschmann, A. Pries, B. Styp-rekowska, P. Hillmeister, L. Loufrani et al., Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flowdriven arteriogenesis, Development, vol.137, pp.2187-2196, 2010.
DOI : 10.1242/dev.045351

URL : http://dev.biologists.org/content/137/13/2187.full.pdf

J. Bussmann, S. A. Wolfe, and A. F. Siekmann, Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling, Development, vol.138, pp.1717-1726, 2011.
DOI : 10.1242/dev.059881

URL : http://dev.biologists.org/content/138/9/1717.full.pdf

Q. Chen, L. Jiang, C. Li, D. Hu, J. W. Bu et al., , 2012.

, Haemodynamics-driven developmental pruning of brain vasculature in zebrafish, PLoS Biol, vol.10, 1001374.

P. Corti, S. Young, C. Y. Chen, M. J. Patrick, E. R. Rochon et al., Interaction between alk1 and blood flow in the development of arteriovenous malformations, Development, vol.138, pp.1573-1582, 2011.

A. S. Forouhar, M. Liebling, A. Hickerson, A. Nasiraei-moghaddam, H. J. Tsai et al., The embryonic vertebrate heart tube is a dynamic suction pump, Science, vol.312, pp.751-753, 2006.

J. B. Freund, J. G. Goetz, K. L. Hill, and J. Vermot, Fluid flows and forces in development: functions, features and biophysical principles, Development, vol.139, pp.1229-1245, 2012.

K. Gaengel, C. Niaudet, K. Hagikura, B. Laviñ-a, L. Muhl et al., The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2, Dev. Cell, vol.23, pp.587-599, 2012.

M. A. Garcia-gonzalez, P. Outeda, Q. Zhou, F. Zhou, L. F. Menezes et al., Pkd1 and Pkd2 are required for normal placental development, PLoS ONE, vol.5, p.5, 2010.

S. P. Herbert and D. Y. Stainier, Molecular control of endothelial cell behaviour during blood vessel morphogenesis, Nat. Rev. Mol. Cell Biol, vol.12, pp.551-564, 2011.

L. Herwig, Y. Blum, A. Krudewig, E. Ellertsdottir, A. Lenard et al., Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo, Curr. Biol, vol.21, pp.1942-1948, 2011.

B. P. Hierck, K. Van-der-heiden, F. E. Alkemade, S. Van-de-pas, J. V. Van-thienen et al., Primary cilia sensitize endothelial cells for fluid shear stress, Dev. Dyn, vol.237, pp.725-735, 2008.

D. A. Hoey, M. E. Downs, and C. R. Jacobs, The mechanics of the primary cilium: an intricate structure with complex function, J. Biomech, vol.45, pp.17-26, 2012.

C. J. Huang, C. T. Tu, C. D. Hsiao, F. J. Hsieh, and H. J. Tsai, Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish, Dev. Dyn, vol.228, pp.30-40, 2003.

C. Iomini, K. Tejada, W. Mo, H. Vaananen, and G. Piperno, Primary cilia of human endothelial cells disassemble under laminar shear stress, J. Cell Biol, vol.164, pp.811-817, 2004.

S. Isogai, M. Horiguchi, and B. M. Weinstein, The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development, Dev. Biol, vol.230, pp.278-301, 2001.

S. Isogai, N. D. Lawson, S. Torrealday, M. Horiguchi, and B. M. Weinstein, Angiogenic network formation in the developing vertebrate trunk, Development, vol.130, pp.5281-5290, 2003.

B. Jung, H. Obinata, S. Galvani, K. Mendelson, B. S. Ding et al., Flowregulated endothelial S1P receptor-1 signaling sustains vascular development, Dev. Cell, vol.23, pp.600-610, 2012.

A. G. Kramer-zucker, F. Olale, C. J. Haycraft, B. K. Yoder, A. F. Schier et al., Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis, Development, vol.132, pp.1907-1921, 2005.

D. W. Laux, S. Young, J. P. Donovan, C. J. Mansfield, P. D. Upton et al., Circulating Bmp10 acts through endothelial Alk1 to mediate flow-dependent arterial quiescence, Development, vol.140, pp.3403-3412, 2013.

F. Le-noble, D. Moyon, L. Pardanaud, L. Yuan, V. Djonov et al., Flow regulates arterial-venous differentiation in the chick embryo yolk sac, Development, vol.131, pp.361-375, 2004.

, Cell Reports, vol.6, pp.799-808, 20142014-03-13.

M. Liebling, A. S. Forouhar, M. Gharib, S. E. Fraser, and M. E. Dickinson, Four-dimensional cardiac imaging in living embryos via postacquisition synchronization of nongated slice sequences, J. Biomed. Opt, vol.10, p.54001, 2005.

J. Mcgrath, S. Somlo, S. Makova, X. Tian, and M. Brueckner, Two populations of node monocilia initiate left-right asymmetry in the mouse, Cell, vol.114, pp.61-73, 2003.

B. Meder, C. Laufer, D. Hassel, S. Just, S. Marquart et al., Circ. Res, vol.104, pp.650-659, 2009.

S. M. Nauli, F. J. Alenghat, Y. Luo, E. Williams, P. Vassilev et al., , 2003.

S. M. Nauli, Y. Kawanabe, J. J. Kaminski, W. J. Pearce, D. E. Ingber et al., , 2008.

S. Nicoli, C. Standley, P. Walker, A. Hurlstone, K. E. Fogarty et al., MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis, Nature, vol.464, pp.1196-1200, 2010.

T. Obara, S. Mangos, Y. Liu, J. Zhao, S. Wiessner et al., Polycystin-2 immunolocalization and function in zebrafish, J. Am. Soc. Nephrol, vol.17, pp.2706-2718, 2006.

E. C. Oh and N. Katsanis, Cilia in vertebrate development and disease, Development, vol.139, pp.443-448, 2012.

M. Potente, H. Gerhardt, C. , and P. , Basic and therapeutic aspects of angiogenesis, Cell, vol.146, pp.873-887, 2011.

B. L. Roman, V. N. Pham, N. D. Lawson, M. Kulik, S. Childs et al., Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels, Development, vol.129, pp.3009-3019, 2002.

S. Rydholm, G. Zwartz, J. M. Kowalewski, P. Kamali-zare, T. Frisk et al., Mechanical properties of primary cilia regulate the response to fluid flow, Am. J. Physiol. Renal Physiol, vol.298, pp.1096-1102, 2010.

J. Schottenfeld, J. Sullivan-brown, and R. D. Burdine, Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw, Development, vol.134, pp.1605-1615, 2007.

A. J. Sehnert, A. Huq, B. M. Weinstein, C. Walker, M. Fishman et al., Cardiac troponin T is essential in sarcomere assembly and cardiac contractility, Nat. Genet, vol.31, pp.106-110, 2002.

W. Supatto and J. Vermot, From cilia hydrodynamics to zebrafish embryonic development, Curr. Top. Dev. Biol, vol.95, pp.33-66, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00841220

M. Tsujikawa and J. Malicki, Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons, Neuron, vol.42, pp.703-716, 2004.

J. Vermot, A. S. Forouhar, M. Liebling, D. Wu, D. Plummer et al., Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart, Current biology: CB, vol.7, pp.93-102, 2009.

S. Yoshiba, H. Shiratori, I. Y. Kuo, A. Kawasumi, K. Shinohara et al., Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2, Science, vol.338, pp.226-231, 2012.

Y. N. Young, M. Downs, and C. R. Jacobs, Dynamics of the primary cilium in shear flow, Biophys. J, vol.103, pp.629-639, 2012.

. Blum, Les cellules de l'embryon en développement font faces à de multiples forces extracellulaires, celles-ci, résultant de flux microscopiques au sein de l'organisateur de l'axe gauche-droite. Les flux créés par les cils organisent l'axe embryonnaire gauche-droite chez la plupart des vertébrés. Les modèles les plus répandus concernant la spécification gauche-droite chez la majorité des vertébrés, Les cils sont impliqués dans de nombreux processus, 2009.

. Gros, Ce flux lent est généré par la rotation de multiples cils motiles localisés à la surface des cellules de l'OGD. Ce flux mène à une réponse collective des cellules qui a lieu spécifiquement du côté droit de l'OGD, ceci est associé à une libération asymétrique de calcium dans les cellules, 2003.

. Essner, Les cils génèrent un flux unidirectionnel en décrivant un mouvement asymétrique dans l'espace (Satir and Christensen, 2007). réduite (Marshall and Kintner, Chez le poisson zèbre, l'organisateur gauche-droite est appelé vésicule de Kupffer (VK) et n'est visible que transitoirement durant la somitogenèse, 2005.

. Borovina, L'orientation spatiale des cils peut être définie par les angles Phi et Theta, ce sont les déterminants majeurs de la force et de la direction du flux créé par les cils. Les mécanismes moléculaires gouvernant l'orientation des cils impliquent des éléments de la voie de signalisation de la polarité planaire cellulaire, l'asymétrie, étant donné qu'elle détermine la force et la direction du flux induit, 2010.

, Le flux de travail expérimental de 3D-Cilia Map peut être divisé en six étapes décrites ci-dessous: ? Étape 1: imagerie 3D in vivo de la VK

?. Étape, Estimation de l'orientation du plan du corps de l'embryon par rapport à l'emplacement de la VK (Fig, vol.2, pp.1-1

, ? Étape 3: position et orientation des cils (Fig, pp.1-1

, ? Étape 5: orientation des angles des cils Phi (?) et Theta (?) en 3D: estimation et histogramme (Fig. 2B1-C2)

, ? Étape 6: carte 2D des caractéristiques des cils et mesure de la densité de surface des cils (Fig, pp.3-4

. En-résumé and . 3d-cilia, Map est une analyse multiscalaire quantitative puissante et rigoureuse des caractéristiques biophysiques des cils (orientation 3D, localisation spatiale et densité), qui pourrait être utilisées dans l'étude d'autres systèmes sphériques ciliés

. Borovina, 2010) incubés pendant 60 minutes dans du Bodipy TR (Molecular Probe) avant l'étape d'imagerie in vivo: le signal de fluorescence a été capté à l'aide de détecteurs hybrides internes à 493-575 nm et 594-730 nm afin de distinguer les cils GFP du signal GFP de la surface des cellules de la VK. (A1) L'ensemble de l'embryon a été imagé à faible résolution spatiale pour estimer les axes embryonnaires: volume de 600µm × 600µm × 150µm comprenant la ligne médiane et la VK de haut en bas avec une taille de voxel de 1,15µm latéralement et 5µm axialement. L'estimation des coordonnées du plan du corps par rapport à l'emplacement de la VK a été effectuée en utilisant le dispositif illustré en (A1) et les trois axes orthogonaux ont été ajustés en 3D à l'aide d'Imaris (Bitplane), lequel point d'intersection est au sein de la VK (A2). L'intersection de chaque axe orthogonal a été utilisé, Manuscrit 2-Fig. 1: Imagerie in vivo et traitement d'image pour extraire la position et l'orientation des cils: Pour obtenir une image suffisamment profonde de l'embryon du poisson zèbre et capturer la vésicule de Kupffer (VK) entière, chaque embryon a été imagé à l'aide d'un microscope SP8 2PEF direct (Leica Inc.) à une longueur d'onde de 930 nm

, Les bases des cils ont été segmentées manuellement à partir de la surface des cellules KV (marques grises dans B2-B3) et son orientation 3D a été estimée (B4), 2011.

, Manuscrit 2-Fig. 2: Estimation de l'angle d'orientation des cils ? et ?: Transformation des coordonnées spatiales selon le plan du corps embryonnaire (A1-A3): répartition spatiale de la position des cils dans le

, Concordance d'un sphéroïde aplati avec la répartition des bases de cils, afin d'enregistrer les données de la VK provenant de différents embryons dans le même cadre (A2)

, Combinaison de données à partir d'embryons différents et affichés dans des histogrammes "rosette" à l'aide de Matlab: rosette de 0 à 360 ° pour ? (C1) et rosette de 0 à 90 ° pour ? (C2), Les cadres de référence dans A1-A3 sont identiques à ceux de B1: eD

, Abréviations: eD = direction dorsale; eL = direction de gauche; eA = direction antérieure. Appendix 3-Extended summary in French

, Manuscrit 2-Fig. 3: Enregistrement des données et représentation sphérique du diagramme de Voronoi pour combiner les caractéristiques des cils de différents embryons et estimer la carte de densité des cils

, A1) et sa transformation avec conservation de la densité de surface (A2). (B) L'état de motilité des cils de différents embryons est représenté dans une carte 2D (cils motiles et immobiles représentés par des points bleues et oranges, respectivement). (C1-2) Estimation de la carte de densité des cils: représentation des distributions des cils dans un diagramme sphérique de Voronoi (C1) à partir duquel on a estimé la surface occupée par le cil individuel et on a obtenu la densité locale des cils (C2)

, Abréviations: eD = direction dorsale; eL = direction de gauche; eA = direction antérieure Appendix 3-Extended summary in French Manuscrit 3-Fig. 4: Développement de profils de flux et orientation des cils au cours du temps de 3 à 9-14 somites (SS): (A) Orientation des cils sur le plan (em, en, ef) au fil du temps (voir Figure 3C). Les vecteurs en noir montrent les orientations des cils d'une vésicule représentative. (B) Débit moyen dans le plan équatorial de la vésicule de Kupffer (KV) calculé à partir de cartes des cils à chaque étape du développement. Le débit moyen est en rotation autour de l'axe DV à tous les stades, devenant plus fort antérieurement à partir de 8-SS

, Appendix 3-Extended summary in French Manuscrit 3-Fig. 7: Limites physiques d'un possible mécanisme de détection latéral, Vitesse angulaire effective (?) comme mesure du flux rotationnel à l'intérieur de la VK au cours temps. La vue de droite du vecteur (?) est illustrée dans les diagrammes principaux, la vue postérieure dans les inserts

M. Beyer, T. Weber, T. Vick, P. Andre, P. Bitzer et al., B-C) Fraction cumulative de cils avec la force d'action antérieure en-dessous (droite, verte) ou au-dessus (gauche, rouge) de la valeur de l'abscisse, Ils doivent être capables de distinguer les flux dirigés antérieurement et postérieurement, vol.238, pp.1215-1225, 2009.

A. Borovina, S. Superina, D. Voskas, C. , and B. , Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia, Nat Cell Biol, vol.12, pp.407-412, 2010.

J. Compagnon, V. Barone, S. Rajshekar, R. Kottmeier, K. Pranjic-ferscha et al., The notochord breaks bilateral symmetry by controlling cell shapes in the zebrafish laterality organ, Dev Cell, vol.31, pp.774-783, 2014.

J. J. Essner, J. D. Amack, M. K. Nyholm, E. B. Harris, and H. J. Yost, Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut, Development, vol.132, pp.1247-1260, 2005.

J. Gros, K. Feistel, C. Viebahn, M. Blum, and C. J. Tabin, Cell movements at Hensen's node establish left/right asymmetric gene expression in the chick, Science, vol.324, pp.941-944, 2009.

B. Guirao, A. Meunier, S. Mortaud, A. Aguilar, J. M. Corsi et al., Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia, Nat Cell Biol, vol.12, p.341, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00555153

M. Hashimoto, K. Shinohara, J. Wang, S. Ikeuchi, S. Yoshiba et al.,

A. , Planar polarization of node cells determines the rotational axis of node cilia, Nat Cell Biol, vol.12, pp.170-176, 2010.

N. Hirokawa, Y. Tanaka, Y. Okada, and S. Takeda, Nodal flow and the generation of left-right asymmetry, Cell, vol.125, pp.33-45, 2006.

P. Leong, C. , and S. , Methods for spherical data analysis and visualization, J Neurosci Methods, vol.80, pp.191-200, 1998.

W. F. Marshall and C. Kintner, Cilia orientation and the fluid mechanics of development, Curr Opin Cell Biol, vol.20, pp.48-52, 2008.

J. Mcgrath, S. Somlo, S. Makova, X. Tian, and M. Brueckner, Two populations of node monocilia initiate left-right asymmetry in the mouse, Cell, vol.114, pp.61-73, 2003.

T. Nakamura, N. Mine, E. Nakaguchi, A. Mochizuki, M. Yamamoto et al., , 2006.

, Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system, Dev Cell, vol.11, pp.495-504

S. Nonaka, Y. Tanaka, Y. Okada, S. Takeda, A. Harada et al., Randomization of leftright asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein, Cell, vol.95, pp.829-837, 1998.

S. Nonaka, S. Yoshiba, D. Watanabe, S. Ikeuchi, T. Goto et al., De novo formation of leftright asymmetry by posterior tilt of nodal cilia, PLoS Biol, vol.3, p.268, 2005.

Y. Okada, S. Takeda, Y. Tanaka, J. C. Izpisua-belmonte, and N. Hirokawa, Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination, Cell, vol.121, pp.633-644, 2005.

P. Satir and S. T. Christensen, Overview of structure and function of mammalian cilia, Annu Rev Physiol, vol.69, pp.377-400, 2007.

H. Song, J. Hu, W. Chen, G. Elliott, P. Andre et al., Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning, Nature, vol.466, pp.378-382, 2010.

W. Supatto and J. Vermot, From cilia hydrodynamics to zebrafish embryonic development, Curr Top Dev Biol, vol.95, p.33, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00841220

S. Yuan, L. Zhao, M. Brueckner, and Z. Sun, Intraciliary calcium oscillations initiate vertebrate left-right asymmetry, 2015.

, Curr Biol, vol.25, pp.556-567