Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, UK.
Department of Industrial Engineering, University of Padua, Padua, Italy.
Nat Mater. 2024 Nov;23(11):1575-1581. doi: 10.1038/s41563-024-01942-9. Epub 2024 Jul 5.
Morphogenesis requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these force fields can lead to congenital malformations. Understanding these dynamic processes requires the quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis. Here we describe elastic spring-like force sensors with micrometre-level resolution, fabricated by intravital three-dimensional bioprinting directly in the closing neural tubes of growing chicken embryos. Integration of calibrated sensor read-outs with computational mechanical modelling allows direct quantification of the forces and work performed by the embryonic tissues. As they displace towards the embryonic midline, the two halves of the closing neural tube reach a compression of over a hundred nano-newtons during neural fold apposition. Pharmacological inhibition of Rho-associated kinase to decrease the pro-closure force shows the existence of active anti-closure forces, which progressively widen the neural tube and must be overcome to achieve neural tube closure. Overall, our approach and findings highlight the intricate interplay between mechanical forces and tissue morphogenesis.
形态发生需要胚胎细胞产生力并进行机械功，以塑造其组织。这些力场的不正确功能会导致先天性畸形。要理解这些动态过程，需要在正在发育的脊椎动物形态发生过程中对三维力学进行量化和分析。在这里，我们描述了弹性弹簧状力传感器，其分辨率达到微米级，通过在生长中的鸡胚闭合神经管内进行活体三维生物打印直接制造而成。校准后的传感器读数与计算力学模型的集成允许直接定量胚胎组织所产生的力和功。当它们向胚胎中线移动时，在神经褶贴附过程中，闭合神经管的两半会达到超过一百毫牛顿的压缩。通过抑制 Rho 相关激酶来减少促闭合力的药理学抑制作用表明存在主动抗闭合力，这些力逐渐扩大神经管，必须克服这些力才能实现神经管闭合。总的来说，我们的方法和发现强调了机械力和组织形态发生之间的复杂相互作用。
