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

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

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.

Keywords: Actomyosin contractility; Branching morphogenesis; Cytoskeleton; Mechanotransduction; Submandibular gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics*
  • Actin Cytoskeleton / ultrastructure
  • Actins / genetics
  • Actins / ultrastructure
  • Actomyosin / genetics*
  • Actomyosin / ultrastructure
  • Acyltransferases / genetics
  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Epithelial Cells / metabolism
  • Epithelium / growth & development
  • Epithelium / metabolism
  • Humans
  • Mechanotransduction, Cellular / genetics
  • Mice
  • Morphogenesis / genetics*
  • Muscle Contraction / genetics*
  • Regeneration / genetics
  • Submandibular Gland / metabolism
  • YAP-Signaling Proteins

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Actomyosin
  • Acyltransferases
  • tafazzin protein, mouse