Mechanical impact of epithelial\u2212mesenchymal transition on epithelial morphogenesis in Drosophila

Mélanie Gracia,Mélanie Gracia,Mélanie Gracia,Mélanie Gracia,Magali Suzanne,Magali Suzanne,Magali Suzanne,Magali Suzanne,Sophie Theis,Sophie Theis,Sophie Theis,Sophie Theis,Guillaume Gay,Corinne Benassayag,Corinne Benassayag,Corinne Benassayag,Corinne Benassayag,Amsha Proag,Amsha Proag,Amsha Proag,Amsha Proag

doi:10.1038/s41467-019-10720-0

Abstract

Epithelial−mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts. Intriguingly, EMT is often associated with tissue invagination during development; however, the impact of EMT on tissue remodeling remain unexplored. Here, we show that at the initiation of the EMT process, cells produce an apico-basal force, orthogonal to the surface of the epithelium, that constitutes an important driving force for tissue invagination in Drosophila. When EMT is ectopically induced, cells starting their delamination generate an orthogonal force and induce ectopic folding. Similarly, during mesoderm invagination, cells undergoing EMT generate an apico-basal force through the formation of apico-basal structures of myosin II. Using both laser microdissection and in silico physical modelling, we show that mesoderm invagination does not proceed if apico-basal forces are impaired, indicating that they constitute driving forces in the folding process. Altogether, these data reveal the mechanical impact of EMT on morphogenesis.

Highlights

Epithelial−mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts
We show that overexpressing the EMT inducer Snail in a group of naive cells from leg imaginal discs was sufficient to recapitulate the hallmarks of EMT including the extrusion from the epithelial sheet or delamination (Fig. 1a), the progressive loss of cell−cell adhesion (Fig. 1b and Supplementary Fig. 1a–c) and the acquisition of migratory properties (Fig. 1c)
Mesoderm invagination is the first morphogenetic movement that takes place in the Drosophila embryo and leads to the formation of a multilayered structure from an initial monolayer blastoderm. It has been initially described as divided in two phases: the first one is ventral furrow formation and includes the successive steps of apical constriction of Snail-expressing ventral cells, which first leads to a change in epithelium curvature, followed by a V-shaped invagination and the formation of a tube of cells that remain attached to each other (Fig. 3a); the second phase corresponds to the loss of epithelial characteristics of mesoderm cells and to their dispersion as they form a monolayer underlying the ectoderm[5]

Summary

Introduction

Epithelial−mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts. We show that at the initiation of the EMT process, cells produce an apico-basal force, orthogonal to the surface of the epithelium, that constitutes an important driving force for tissue invagination in Drosophila. During mesoderm invagination, cells undergoing EMT generate an apico-basal force through the formation of apicobasal structures of myosin II Using both laser microdissection and in silico physical modelling, we show that mesoderm invagination does not proceed if apico-basal forces are impaired, indicating that they constitute driving forces in the folding process. We induce EMT ectopically in a naive tissue (leg imaginal disc) by ectopic Snail expression In this context, we observe that prior to delamination, each cell maintains strong cell−cell adhesion and generates a force orthogonal to the apical surface leading to the deformation of the epithelium around the collapsing apex. Before their delamination, they generate forces orthogonal to the plane of the epithelium, and actively participate in tissue folding

Methods

Results

Conclusion