title: Mechanotransduction in mechanically coupled pulsating cells: transition to collective constriction and mesoderm invagination simulation.
abstract: Embryonic differentiation and morphogenesis require the coordination of the cascades of gene product expression with the morphogenetic sequence of development. The influence of mechanical deformations driven by morphogenetic movements on biochemical activities was recently revealed by the existence of mechanotransduction processes in development, involving both gene transcription and protein behaviour. In the early Drosophila embryo, apical stabilization of Myosin-II leading to mesoderm invagination at the onset of gastrulation was proposed to be triggered in response to the activation of the Fog mechanotransduction pathway by the Snail-dependent active mechanical oscillations of cell apex sizes. Here we simulate the mesoderm as mechanically coupled cells, with pulsatile forces of constriction at the cell level mimicking Snail-dependent active fluctuations of apexes. We define a critical apex diameter triggering active constriction that mimics the activation of the Fog mechanotransduction pathway leading to cell constriction. We find that collective movements trigger the dynamical transition to constriction predicting the experimental dynamics of mesoderm cell apex size decrease with a modulus of contractility four times higher than the passive modulus of elastic deformation of the cells. The contraction wave is activated in a pulsation frequency-dependent process, and propagates at multicellular scales through local cell-cell mechanical interactions. By reproducing the pattern of Snail and Fog gene product protein expression in a simulation of ventral cells, the model phenocopies the pattern of Myo-II apical stabilization, and the dynamic pattern of constriction that initiates along a central sub-domain of the mesoderm. We propose that multicellular mechanical collective effects couple with mechanotransduction biochemical mechanisms to trigger the transition of collective coordinated constriction, through a mechano-genetic process ensuring efficient and regular mesoderm invagination.
authors: Mechanics and Genetics of Embryonic and Tumoral Development Group, Institut Curie, Paris, France.
authors: Benjamin
authors: B
authors: Driquez
authors: Adrien
authors: A
authors: Bouclet
authors: Emmanuel
authors: E
authors: Farge
mesh_terms: D000818:Animals; D019521:Body Patterning; D003198:Computer Simulation; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D040542:Mechanotransduction, Cellular; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C508614:FOG protein, Drosophila; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C000604451:sna protein, Drosophila; D024462:Myosin Type II