Arp2/3-dependent mechanical control of morphogenetic robustness in an inherently challenging environment

Dev Cell. 2021 Mar 8;56(5):687-701.e7. doi: 10.1016/j.devcel.2021.01.005. Epub 2021 Feb 2.

Abstract

Epithelial sheets undergo highly reproducible remodeling to shape organs. This stereotyped morphogenesis depends on a well-defined sequence of events leading to the regionalized expression of developmental patterning genes that finally triggers downstream mechanical forces to drive tissue remodeling at a pre-defined position. However, how tissue mechanics controls morphogenetic robustness when challenged by intrinsic perturbations in close proximity has never been addressed. Using Drosophila developing leg, we show that a bias in force propagation ensures stereotyped morphogenesis despite the presence of mechanical noise in the environment. We found that knockdown of the Arp2/3 complex member Arpc5 specifically affects fold directionality while altering neither the developmental nor the force generation patterns. By combining in silico modeling, biophysical tools, and ad hoc genetic tools, our data reveal that junctional myosin II planar polarity favors long-range force channeling and ensures folding robustness, avoiding force scattering and thus isolating the fold domain from surrounding mechanical perturbations.

Keywords: Myosin II planar polarity; force transmission; invagination; mechanical noise; morphogenesis robustness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Animals
  • Cell Polarity*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Morphogenesis*
  • Myosin Type II / genetics
  • Myosin Type II / metabolism*

Substances

  • Actin-Related Protein 2-3 Complex
  • Drosophila Proteins
  • Myosin Type II