How to build a retina. (360G-Wellcome-100329_Z_12_Z)

Fascinated by how an organ as complex and refined as the brain is made through instructions encoded in DNA, I focus on the retina, perhaps the most experimentally tractable part of the brain (Figure 1). Three basic and interrelated questions form the core of this proposal: 1. Vertebrate species have different sized retinas. What mechanisms regulate the appropriate number of neurons generated from a population of retinal progenitor cells (RPCs) that themselves produce variable numbers of desce ndant neurons? 2. In all vertebrates, retinal cells consist of six main types and more than 50 subtypes. How are these types and subtypes generated in the correct proportions? 3. A conserved feature of retinal development is histogenesis, the relationship between cell birth, cell type, and tissue architecture. How is this achieved? Breakthroughs in time-lapse imaging, molecular biology and quantitative analysis allow us now to address these fundamental yet unsolved questions. Answer s to them should reach beyond the retina to other developmental systems, particularly the brain. We hope to resolve molecular regulatory pathways that underlie these processes and discover mechanisms that unify and coordinate proliferation, cell fate determination and tissue architecture.