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Theses

Contrôle spatio-temporel de l'activité de l'acide rétinoïque dans le rhombencephale du poisson zèbre

Abstract : The aim of my thesis is to study the spatio-temporal control of gene expression induced by retinoic acid (RA) in the zebrafish embryo. Retinoic acid is a morphogen derivative of vitamin A, which is involved in many processes during embryonic development. In vertebrates, this molecule plays a crucial role in the establishment of the anterior-posterior and dorsal-ventral axis as well as the segmentation of hindbrain by the formation of a gradient antero-posterior resulting in differential expression of Hox genes. The natural isomers of retinoic acid such as all-trans retinoic acid (ATRA) and 9-cis RA 13-cis RA are part of the signaling pathway of RA. This pathway is mediated by two subtypes of nuclear receptors: RAR and RXR act as transcription factors. Isomers of retinoic acid have different affinities for the two receptor types. The 9-cis RA is able to bind to RARs or RXRs. ATRA is the principal form of retinoic acid in the living organism, and is the ligand for RAR. 13-cis RA is also capable of binding to RAR but its affinity is very low compared to ATRA. With this low affinity for RAR, 13-cis RA has been used to treat acne and leukemia to minimize the effects tetrogenic ATRA. In vitro, the 13-cis RA is able to isomerize rapidly into ATRA after UV illumination. This isomerization is also possible in the opposite direction; we can illuminate ATRA to turn it into 13-cis-RA. Using this chemical property of retinoic acid, I have developed a method that allows activatation or inactivation of retinoic acid by UV illumination with high spatio-temporal resolution in a living organism.
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https://tel.archives-ouvertes.fr/tel-00836933
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Submitted on : Friday, June 21, 2013 - 5:49:59 PM
Last modification on : Thursday, October 29, 2020 - 3:01:40 PM
Long-term archiving on: : Sunday, September 22, 2013 - 4:11:35 AM

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  • HAL Id : tel-00836933, version 1

Citation

Lijun Xu. Contrôle spatio-temporel de l'activité de l'acide rétinoïque dans le rhombencephale du poisson zèbre. Biochimie [q-bio.BM]. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66550⟩. ⟨tel-00836933⟩

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