Cross-linker-mediated regulation of actin network organization controls tissue morphogenesis

J Cell Biol. 2019 Aug 5;218(8):2743-2761. doi: 10.1083/jcb.201811127. Epub 2019 Jun 28.

Abstract

Contraction of cortical actomyosin networks driven by myosin activation controls cell shape changes and tissue morphogenesis during animal development. In vitro studies suggest that contractility also depends on the geometrical organization of actin filaments. Here we analyze the function of actomyosin network topology in vivo using optogenetic stimulation of myosin-II in Drosophila embryos. We show that early during cellularization, hexagonally arrayed actomyosin fibers are resilient to myosin-II activation. Actomyosin fibers then acquire a ring-like conformation and become contractile and sensitive to myosin-II. This transition is controlled by Bottleneck, a Drosophila unique protein expressed for only a short time during early cellularization, which we show regulates actin bundling. In addition, it requires two opposing actin cross-linkers, Filamin and Fimbrin. Filamin acts synergistically with Bottleneck to facilitate hexagonal patterning, while Fimbrin controls remodeling of the hexagonal network into contractile rings. Thus, actin cross-linking regulates the spatio-temporal organization of actomyosin contraction in vivo, which is critical for tissue morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Actomyosin / metabolism
  • Animals
  • Cross-Linking Reagents / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism*
  • Elasticity
  • Embryo, Nonmammalian / metabolism
  • Gastrulation
  • HeLa Cells
  • Humans
  • Models, Biological
  • Morphogenesis*
  • Mutation / genetics
  • Myosin Type II / metabolism
  • Optogenetics
  • Phenotype
  • Protein Domains

Substances

  • Actins
  • Cross-Linking Reagents
  • Drosophila Proteins
  • Actomyosin
  • Myosin Type II

Associated data

  • GENBANK/AAC46467