Evolutionary implication of mechanotransduction in development

Abstract : In this thesis, I first focused on the testing of the hypothesis of the mechanotransductive activation of the apical accumulation of Myosin-II (Myo-II) that leads to Drosophila embryos mesoderm invagination, in response to the active cell apex pulsations preceding gastrulation in the mesoderm. This hypothesis was proposed on the basis of previous experiments realized in my host lab, having consisted in the rescue of mesoderm invagination in pulsation and invagination defective mutants, in response to a simple mechanical indent of the mesoderm. Here I demonstrated quantitatively the plausibility of such mechanical trigger of the active apical accumulation of Myo-II leading to subsequent mesoderm invagination, in response to the mechanical strains developed by the endogenous pulsative movements of mesoderm cell apexes, in silico. In a second part, I tested experimentally the role of the mechanical strains developed by the very first morphogenetic movements of zebrafish (Danio rerio) and Drosophila embryos, in the early specification of mesoderm cells identity. Specifically, to test this hypothesis, I developed magnetic biophysical tools to mimic the epiboly morphogenetic movements in epiboly defective zebrafish embryos. We found the beta-catenin (B-cat) Y667 phosphorylation as the common mechano-transductive pathway involved in earliest mesoderm genes expression notail and twist respectively, in response to the very first morphogenetic movements of embryogenesis in both species, epiboly and mesoderm invagination, respectively. This allowed to suggest such mechanotransduction pathway as conserved from the last common ancestor of both species, namely the last common ancestor of bilaterians, therefore possibly involved in the origins of mesoderm emergence in the ancestor, which represents a currently important opened question of evo-devo. In a third part, I developed experiments of mechanical indent of Drosophila embryos germ cells, and demonstrated the production of generational heritable developmental defects induced on at least 3 generations. These experiments suggest accidental mechanical perturbation of germ cells as a putative new motor mode of heritable modulations in the genetic developmental program of embryogenesis, with the molecular mechanism underlying such transmission being currently in progress.
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Adrien Bouclet. Evolutionary implication of mechanotransduction in development. Biological Physics [physics.bio-ph]. Université René Descartes - Paris V, 2014. English. ⟨NNT : 2014PA05T019⟩. ⟨tel-01071238⟩

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