Department of Molecular Medicine, University of Padua, Padua, Italy; IFOM ETS, the AIRC Institute of Molecular Oncology, Italy.
Department of Molecular Medicine, University of Padua, Padua, Italy.
Dev Biol. 2022 Aug;488:54-67. doi: 10.1016/j.ydbio.2022.05.005. Epub 2022 May 14.
Myriads forces are at play during morphogenesis. Their concerted activity shapes individual cells, tissues and the whole embryo, representing the most awe-inspiring marvel of developmental biology. In spite of their prevalence, the potential instructive role of cell mechanics in fate determination and patterning has remained long neglected, in part due to the difficulties in translating the physical world of cells in molecular terms. The recent discovery of the principles of mechanotransduction, of how these impact on gene expression, is however starting to change this scenario, making mechanotransduction finally amenable to experimental dissection through genetics, molecular and bioengineering approaches. Here we review this emerging field, and a series of discoveries that potently bring back cell mechanics at the centerstage of vertebrate developmental biology. We discuss the role of actomyosin contractility as integrating platform between morphogens, lateral inhibition and mechanosignaling. We also review data indicating that supracellular pulling forces, coupled with solid-to-fluid changes in the material contexture of embryonic fields, may act as overarching mechanical "organizers". The evidence also indicates that a continuum of forces is what ultimately locks "self-organizing" movements with cell fate, from the earliest pre-implantation decisions to the fine details of organogenesis. Notably, similar mechanisms are reawakened in organoids and in adult tissues during regeneration. Developmental biology has been correctly depicted, but recently often forgotten, as the "mother" of all biological disciplines. Investigations in developmental mechanics may revamp interest, and have a broad impact in the fields of regenerative medicine, stem cells and cancer biology.
在形态发生过程中，无数力量在起作用。它们的协同活动塑造了个体细胞、组织和整个胚胎，代表了发育生物学最令人惊叹的奇迹。尽管它们很普遍，但细胞力学在命运决定和模式形成中的潜在指导作用长期以来一直被忽视，部分原因是难以将细胞的物理世界转化为分子术语。然而，最近发现了机械转导的原理，以及这些原理如何影响基因表达，这正在开始改变这种情况，使得机械转导最终可以通过遗传学、分子和生物工程方法进行实验剖析。在这里，我们回顾了这个新兴领域，以及一系列强有力的发现，这些发现使细胞力学重新成为脊椎动物发育生物学的中心舞台。我们讨论了肌动球蛋白收缩作为形态发生因子、侧向抑制和机械信号之间的整合平台的作用。我们还回顾了表明超细胞牵拉力与胚胎场材料结构的固液变化相结合可能作为机械“组织者”的作用的数据。证据还表明，从最早的着床前决定到器官发生的精细细节，一系列力最终将“自我组织”的运动与细胞命运锁定在一起。值得注意的是，类似的机制在类器官和成年组织的再生过程中被重新唤醒。发育生物学被正确地描绘为所有生物学学科的“母亲”，但最近经常被遗忘。发育力学的研究可能会重新激发人们的兴趣，并在再生医学、干细胞和癌症生物学等领域产生广泛影响。
