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Genetic Determinants of Retinal Cell Development

Abstract

The central nervous system, is composed of several complex tissues that serve a wide variety of critical functions. One of these tissues residing in the eye, the retina, serves to convert incoming photons of light to neural signals that aid in the perception of vision. The retina is comprised of various cellular populations that each develop through unique set of mechanisms, many of which remained to be elucidated. In this dissertation, we have examined the genetic mechanisms underlying how specific populations of cells in the retina develop, in order to more fully understand how individual populations arise and therefore gain insight into how these populations may interact with one another in the mature retina. First, we sought to uncover genes that modulate neuronal cell number. Through the use of a forward genetic screen, we were able to study the development of the mouse retina across genetically dissimilar strains and identify genes that modulate retinal development. We uncovered a role for two novel genes, Xkr8 and Ggct, in the modulation of bipolar cell number and pursued an investigation into the genetic variants underlying cell number differences across inbred mouse strains. Secondly, we sought to elucidate novel mechanisms by how the glial population of astrocytes develop. We identified an unknown function for the gene Sox2 in the development of astrocytes as well as the retinal vasculature. Taken together, these analyses provide insight into how both neuronal and glial cell populations develop in the mouse retina. Both of these cellular populations are critical to a functioning retina and by understanding the specific mechanisms underlying how they develop, we begin to uncover how the complexity of the central nervous system arises.

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