Mechanical Function of the Nucleus in Force Generation during Epithelial Morphogenesis

Dev Cell. 2019 Jul 22;50(2):197-211.e5. doi: 10.1016/j.devcel.2019.05.027. Epub 2019 Jun 13.

Abstract

Mechanical forces are critical regulators of cell shape changes and developmental morphogenetic processes. Forces generated along the epithelium apico-basal cell axis have recently emerged as essential for tissue remodeling in three dimensions. Yet the cellular machinery underlying those orthogonal forces remains poorly described. We found that during Drosophila leg folding cells eventually committed to die produce apico-basal forces through the formation of a dynamic actomyosin contractile tether connecting the apical surface to a basally relocalized nucleus. We show that the nucleus is anchored to basal adhesions by a basal F-actin network and constitutes an essential component of the force-producing machinery. Finally, we demonstrate force transmission to the apical surface and the basal nucleus by laser ablation. Thus, this work reveals that the nucleus, in addition to its role in genome protection, actively participates in mechanical force production and connects the contractile actomyosin cytoskeleton to basal adhesions.

Keywords: Drosophila; LINC; Live imaging; Talin; actomyosin; apoptosis; basal adhesion; linker of nucleoskeleton and cytoskeleton complex; mechanical forces; morphogenesis; nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Actomyosin / metabolism*
  • Animals
  • Apoptosis
  • Cell Adhesion
  • Cell Nucleus / physiology*
  • Cytoskeleton / physiology*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Epithelium / growth & development
  • Epithelium / physiology*
  • Female
  • Male
  • Morphogenesis*

Substances

  • Actins
  • Actomyosin