Optic cup morphogenesis: a model to study the cellular and molecular bases of basal constriction

Abstract

Shaping the vertebrate eye into a hemispherical organ requires the inward folding of the polarized retinal neuroepithelium. Optic cup morphogenesis is however an atypical model for epithelial morphogenesis. In contrast to well-known apical constrictions described in Drosophila epithelia, it involves the contraction of the tissue towards its basal surface. Understanding which cellular and molecular aspects of basal constriction are specific and which are shared with apical constrictions is a long-term objective in the laboratory. In particular we focus on developmental regulators that, operating directly on basic cell properties, such as cell adhesion, cell shape or cell contractility, control eye morphogenesis. One of these developmental effectors, the transmembrane regulator of polarized integrin endocytosis Opo, plays an essential role in optic cup formation and hence it has been a main research topic in our group. Through a combination of transcriptomic, genetic, and cell biological approaches, we are currently identifying novel components of the molecular machinery involved in optic cup folding. Here we explore the mechanisms coupling the activation of the retinal gene regulatory network to the constriction-driven folding of the retinal epithelium. We show that which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.