Fernandez-Sanchez Maria-Elena, Serman Fanny, Ahmadi Padra, Farge Emmanuel
Mechanics and Genetics of Embryonic and Tumoral Development group, UMR168 CNRS, Institut Curie, 11 rue Pierre et Marie Curie, F-75005, Paris, France.
Methods Cell Biol. 2010;98:295-321. doi: 10.1016/S0091-679X(10)98012-6.
Embryonic development is a coordination of multicellular biochemical patterning and morphogenetic movements. Last decades revealed the close control of myosin-II-dependent biomechanical morphogenesis by patterning gene expression, with constant progress in the understanding of the underlying molecular mechanisms. Reversed control of developmental gene expression and of myosin-II patterning by the mechanical strains developed by morphogenetic movements was recently revealed at Drosophila gastrulation, through mechanotransduction processes involving the Armadillo/beta-catenin and the downstream of Fog Rho pathways. Here, we present the theoretical (simulations integrating the accumulated knowledge in the genetics of early embryonic development and morphogenesis) and the experimental (genetic and biophysical control of morphogenetic movements) tools having allowed the uncoupling of pure genetic inputs from pure mechanical inputs in the regulation of gene expression and myosin-II patterning. Specifically, we describe the innovative magnetic tweezers tools we have set up to measure and apply physiological strains and forces in vivo, from the inside of the tissue, to modulate and mimic morphogenetic movements in living embryos. We discuss mechanical induction incidence in tumor development and perspective in evolution.
胚胎发育是多细胞生物化学模式形成与形态发生运动的协同过程。过去几十年揭示了通过模式基因表达对肌球蛋白II依赖的生物力学形态发生进行密切控制，在对潜在分子机制的理解上不断取得进展。最近在果蝇原肠胚形成过程中，通过涉及犰狳/β-连环蛋白和Fog Rho途径下游的机械转导过程，揭示了形态发生运动产生的机械应变对发育基因表达和肌球蛋白II模式形成的反向控制。在此，我们展示了理论工具（整合早期胚胎发育和形态发生遗传学中积累知识的模拟）和实验工具（形态发生运动的遗传和生物物理控制），这些工具能够在基因表达调控和肌球蛋白II模式形成中，将纯遗传输入与纯机械输入解耦。具体而言，我们描述了我们建立的创新型磁镊工具，用于在体内从组织内部测量和施加生理应变与力，以调节和模拟活胚胎中的形态发生运动。我们讨论了机械诱导在肿瘤发展中的影响以及在进化方面的前景。
