PROJECT SUMMARY This proposal is a renewal application for R01 EY012549 entitled "Cell-Cell Signaling in Embryonic and Retinal Development". The question of how complex tissues like the eye achieve the cellular organization and three-dimensional form required for vision is of fundamental importance to understanding both normal developmental progression and disease mechanisms that perturb cell shapes, structures and patterns. A great deal is known about the genetically controlled terminal differentiation programs that produce the specialized cytoskeletal structures, cell-cell junctional adhesions and cell-extracellular matrix contacts unique to each retinal cell type. How the resulting cell shapes, structures and connections introduce physical constraints that influence final organ shape and function is not well-studied. This is particularly critical to a complex organ like the eye, because the organization of its diverse and highly specialized cell types must be precise to support vision. The goal of this proposal is to understand the cellular and tissue-scale properties and interactions that together sculpt the final form of the Drosophila compound eye. The fly retina provides a superbly tractable and well- defined experimental model, with a proven track record in uncovering conserved mechanisms. The stereotyped patterning and architecture of the fly retina facilitates the identification and tracking of individual cell types over space and time, and the wealth of available markers permits detailed analysis and quantification of cell shapes, structures, interactions and tissue-level patterns. Improving our understanding of fundamental morphogenetic processes has relevance not only to normal development and regenerative biology, but also to considering how disease-associated defects in one cell type or in one organ may influence adjacent cell types or organs. Thus, the knowledge gained from the studies described in this proposal will improve understanding of an important area of developmental biology and impact human health. Aim 1 will investigate how interactions between different retinal cell types elaborate and maintain the precise 3D tissue organization and structure required for vision. Our hypothesis is that cell-cell and cell-ecm interactions provide redundant mechanical coupling that organizes pattern, drives cellular differentiation and ensures robustness of the retinal morphogenetic program. Aim 2 will explore how tissue-intrinsic properties and the retinal-extrinsic environment contribute to the establishment and maintenance of retinal curvature, a tissue-level property critical for vision. We hypothesize that the pupal retina transitions from an initial “floppy” or viscous-like state that can be influenced by its physical environment to a rigid or elastic solid-like state that can autonomously support tissue shape.