Cell proliferation and Notch signaling coordinate the formation of epithelial folds in theDrosophilaleg

Abstract

SummaryThe formation of complex three-dimensional organs during development requires the precise coordination between patterning networks and mechanical forces. In particular, tissue folding is a crucial process that relies on a combination of local and tissue-wide mechanical forces. Here, we investigate the contribution of cell proliferation to epithelial morphogenesis using theDrosophilaleg tarsal folds as a model. We reveal that tissue-wide compression forces generated by cell proliferation, in coordination with Notch signaling pathway, are essential for the formation of epithelial folds in precise locations along the proximo-distal axis of the leg. As cell numbers increase, compressive stresses arise, promoting the buckling of the epithelium and reinforcing the apical constriction of invaginating cells. Additionally, the Notch targetdysfusion(dysf) plays a key function specifying the location of the folds, through the apical accumulation of F-actin and the apico-basal shortening of invaginating cells. These findings provide new insights into the intricate mechanisms involved in epithelial morphogenesis, highlighting the critical role of tissue-wide forces in shaping a three-dimensional organ in a reproducible manner.