Zebrafish <italic>Rx</italic>, a paired -class homeobox gene, and retinal development.

The paired-class homeobox gene, Rx, is essential for vertebrate eye development. Targeted disruption of the Rx gene completely blocks formation of the optic primordia and produces forebrain abnormalities in mouse embryos while overexpression of Rx leads to formation of ectopic retinal tissue and duplication of retina and forebrain in Xenopus. In my thesis research I used zebrafish as a model organism to study the function of Rx in retinal development. First, I analyzed expression patterns of three zebrafish Rx genes (rx1, rx2, rx3) in embryos and adults. All three genes show dynamic spatiotemporal patterns of expression and initially their expression domains are coextensive with the region in the anterior neural plate identified as the retinal field by published fate mapping studies. As development proceeds, the expression of rx1/2 is restricted to the neural retina while the expression of rx3 can also be detected in the hypothalamus. In the differentiated neural retina, rx1/2 are expressed only in the cone photoreceptors and marginal germinal zone whereas rx3 is expressed in the bipolar cells. Using rx as a marker for retinal precursors and emx1 or BF-1 as a marker for telencephalic precursors, I demonstrated that the separation of the retinal field and/or the formation of bilateral optic primordia probably require relative cell movements between forebrain and retinal precursors. Overexpression of either rx1 or rx2 but not rx3 results in the loss of forebrain tissue and the ectopic formation of retinal tissue. The mechanism involves changes of cell fates based on following observations. Increased cell death is not associated with the loss of forebrain and the ectopic expression of retinal marker is not associated with the increase of mitotic cells. In addition, changes of gene expression patterns are evident in embryos with ectopic rx2 at neural keel stage. Results from deletion constructs experiments further suggest that rx2 may require cofactors) to promote retinal development. These data not only reveal the mechanism that may lead to the formation of bilateral optic primordia but also suggest that regulated expression of zebrafish rx1 and rx2 helps to define the region of the forebrain fated to give rise to retinal tissue.Ph.D.Biological SciencesNeurosciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125023/2/3016824.pd