Retinal Pigment Epithelium and Neural Retinal Progenitors Interact Via Semaphorin 6D to Facilitate Optic Cup Morphogenesis

Abstract

Cell movement propels embryonic tissues to acquire shapes required for mature function. The movements are driven both by acto-myosin signaling, and by cells interacting with the extracellular matrix. Unknown is whether cell-cell interactions within a tissue are also required, and the molecular mechanisms by which such communication might occur. Here we use the developing visual system of zebrafish as a model to understand the role cell-cell communication plays in tissue morphogenesis in the embryonic nervous system. We identify that cell-cell mediated contact between two distinct cell populations, progenitors of the neural retina and retinal pigment epithelium, facilitates epithelial flow to produce the mature cupped retina. We identify for the first time the need in eye morphogenesis for distinct populations of progenitors to interact, and suggest a novel role for a member of a key developmental signaling family, the transmembrane Semaphorin6d, as mediating communication between distinct cell types to control tissue morphogenesis.

Significance Statement

We identify that cell-cell communication between neural progenitors in the embryonic eye and their non-neural, retinal pigmented epithelial cell neighbours promotes the cell movements which are required to form a cupped retina that mediates vision. We also reveal the repulsive guidance molecule Semaphorin6d as the molecular mechanism that allows these two distinct cell populations to work together to orchestrate optic cup morphogenesis.