Numb/Numbl-Opo Antagonism Controls Retinal Epithelium Morphogenesis by Regulating Integrin Endocytosis

SummaryPolarized trafficking of adhesion receptors plays a pivotal role in controlling cellular behavior during morphogenesis. Particularly, clathrin-dependent endocytosis of integrins has long been acknowledged as essential for cell migration. However, little is known about the contribution of integrin trafficking to epithelial tissue morphogenesis. Here we show how the transmembrane protein Opo, previously described for its essential role during optic cup folding, plays a fundamental role in this process. Through interaction with the PTB domain of the clathrin adaptors Numb and Numbl via an integrin-like NPxF motif, Opo antagonizes Numb/Numbl function and acts as a negative regulator of integrin endocytosis in vivo. Accordingly, numb/numbl gain-of-function experiments in teleost embryos mimic the retinal malformations observed in opo mutants. We propose that developmental regulator Opo enables polarized integrin localization by modulating Numb/Numbl, thus directing the basal constriction that shapes the vertebrate retina epithelium.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (302 K)Download as PowerPoint slideHighlights► The morphogenetic regulator Opo interacts with Numb/Numbl clathrin adaptors ► Opo is a negative developmental regulator of integrin endocytosis ► Opo enables normal integrin localization by keeping Numb/Numbl in check ► Polarized integrin endocytosis plays a key role during optic cup morphogenesis