Mechanical Function of the Nucleus in Force Generation during Epithelial Morphogenesis

Arnaud Ambrosini,Mégane Rayer,Bruno Monier,Magali Suzanne

doi:10.1016/j.devcel.2019.05.027

Abstract

SummaryMechanical 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.

Highlights

Animal development relies on the dynamic remodeling of tissues to create germ layers
Apical constriction of epithelial cells is usually associated with tissue invagination and is thought to trigger tissue remodeling (Martin and Goldstein, 2014)
Force generation at the cell scale necessiosin structure that forms along the apico-basal cell axis of dying tates that the intracellular molecular force-producing machinery cells

Summary

Introduction

Animal development relies on the dynamic remodeling of tissues to create germ layers. During gastrulation, it allows to segregate tissues with distinct fate (Keller et al, 2003) Another example is neural tube formation in vertebrates, which relies on local bending and closure of the neural plate, and failure to correctly invaginate may lead to developmental defects such as spina bifida or anencephaly associated with defective neural tube formation (Colas and Schoenwolf, 2001). Much of our understanding comes from the fine characterization of the early steps of Drosophila mesoderm invagination In this case, a pulsatile actomyosin network accumulates medio-apically in invaginating cells (Martin et al, 2009; Mason et al, 2013). Transient contraction of the actomyosin network causes a decrease in apical surface area that is stabilized by a ratchet mechanism while forces are transmitted to neighbors through adherens junctions (Martin et al, 2009, 2010). Additional mechanisms, such as junctional rather than medio-apical accumulation of actomyosin, enable apico-basal force generation (Hildebrand, 2005; Owaribe et al, 1981)

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