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通过组织间摩擦和主动应力塑造斑马鱼肌节。

Shaping the zebrafish myotome by intertissue friction and active stress.

机构信息

Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

Department of Biological Sciences, National University of Singapore, Singapore 117411, Singapore.

出版信息

Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25430-25439. doi: 10.1073/pnas.1900819116. Epub 2019 Nov 26.

Abstract

Organ formation is an inherently biophysical process, requiring large-scale tissue deformations. Yet, understanding how complex organ shape emerges during development remains a major challenge. During zebrafish embryogenesis, large muscle segments, called myotomes, acquire a characteristic chevron morphology, which is believed to aid swimming. Myotome shape can be altered by perturbing muscle cell differentiation or the interaction between myotomes and surrounding tissues during morphogenesis. To disentangle the mechanisms contributing to shape formation of the myotome, we combine single-cell resolution live imaging with quantitative image analysis and theoretical modeling. We find that, soon after segmentation from the presomitic mesoderm, the future myotome spreads across the underlying tissues. The mechanical coupling between the future myotome and the surrounding tissues appears to spatially vary, effectively resulting in spatially heterogeneous friction. Using a vertex model combined with experimental validation, we show that the interplay of tissue spreading and friction is sufficient to drive the initial phase of chevron shape formation. However, local anisotropic stresses, generated during muscle cell differentiation, are necessary to reach the acute angle of the chevron in wild-type embryos. Finally, tissue plasticity is required for formation and maintenance of the chevron shape, which is mediated by orientated cellular rearrangements. Our work sheds light on how a spatiotemporal sequence of local cellular events can have a nonlocal and irreversible mechanical impact at the tissue scale, leading to robust organ shaping.

摘要

器官形成是一个固有的生物物理过程,需要大规模的组织变形。然而,理解复杂的器官形状如何在发育过程中出现仍然是一个主要的挑战。在斑马鱼胚胎发生过程中,大的肌肉段,称为肌节,获得了一种特征性的人字形形态,这被认为有助于游泳。肌节的形状可以通过在形态发生过程中干扰肌肉细胞分化或肌节与周围组织之间的相互作用来改变。为了理清导致肌节形状形成的机制,我们将单细胞分辨率的实时成像与定量图像分析和理论建模相结合。我们发现,在从体节前中胚层分离后不久,未来的肌节就会在下面的组织上扩散开来。未来的肌节和周围组织之间的机械耦合似乎在空间上有所不同,这有效地导致了空间异质摩擦。我们使用一个顶点模型并结合实验验证,表明组织扩展和摩擦的相互作用足以驱动人字形形状形成的初始阶段。然而,在野生型胚胎中,局部各向异性的应力,在肌肉细胞分化过程中产生,是形成人字形锐角所必需的。最后,组织可塑性是形成和维持人字形形状所必需的,这是通过定向的细胞重排来介导的。我们的工作揭示了局部细胞事件的时空序列如何在组织尺度上产生非局部和不可逆的机械影响,从而导致强健的器官形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c016/6925982/239df2375075/pnas.1900819116fig01.jpg

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