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肌动球蛋白复合物在上皮器官分支形态发生中的机械发生作用。

A mechanogenetic role for the actomyosin complex in branching morphogenesis of epithelial organs.

机构信息

Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 08826, Republic of Korea

Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

出版信息

Development. 2021 Mar 23;148(6):dev190785. doi: 10.1242/dev.190785.

DOI:10.1242/dev.190785
PMID:33658222
Abstract

The actomyosin complex plays crucial roles in various life processes by balancing the forces generated by cellular components. In addition to its physical function, the actomyosin complex participates in mechanotransduction. However, the exact role of actomyosin contractility in force transmission and the related transcriptional changes during morphogenesis are not fully understood. Here, we report a mechanogenetic role of the actomyosin complex in branching morphogenesis using an organotypic culture system of mouse embryonic submandibular glands. We dissected the physical factors arranged by characteristic actin structures in developing epithelial buds and identified the spatial distribution of forces that is essential for buckling mechanism to promote the branching process. Moreover, the crucial genes required for the distribution of epithelial progenitor cells were regulated by YAP and TAZ through a mechanotransduction process in epithelial organs. These findings are important for our understanding of the physical processes involved in the development of epithelial organs and provide a theoretical background for developing new approaches for organ regeneration.

摘要

肌球蛋白复合体通过平衡细胞成分产生的力,在各种生命过程中发挥着关键作用。除了其物理功能外,肌球蛋白复合体还参与了机械转导。然而,肌球蛋白收缩在力传递中的精确作用以及形态发生过程中相关的转录变化尚不完全清楚。在这里,我们使用小鼠胚胎下颌下腺的器官培养系统报告了肌球蛋白复合体在分支形态发生中的一种遗传机械作用。我们剖析了发育中的上皮芽中特征性肌动蛋白结构排列的物理因素,并确定了对于促进分支过程的卷曲机制至关重要的力的空间分布。此外,上皮祖细胞分布所必需的关键基因通过上皮器官中的机械转导过程受到 YAP 和 TAZ 的调节。这些发现对于我们理解涉及上皮器官发育的物理过程很重要,并为开发新的器官再生方法提供了理论基础。

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