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Show THE ROLE OF INK4D IN REGULATING RETINAL PROGENITOR CELL PROLIFERATION IN THE CHX10 NULL RETINA Billie Bixby, (Edward Levine) Department of Ophthalmology and Visual Sciences, Moran Eye Institute ChxlO is a homeodomain transcription factor expressed in reti- nal progenitor cells (RPCs) and null mutations in the ChxlO gene cause congenital micropthalmia, or small eyes, in humans and mice. This defect in proliferation is due, in large part, to a reduc-tion in RPC proliferation during eye development. To better eluci-date the mechanisms by which ChxlO regulates proliferation, cell cycle proteins important for RPC proliferation have been identified and examined to see if they interact with ChxlO to help regulate retinal cell number. Kipl and Ink4d are two cyclin-dependent ki- nase inhibitors that have been shown to negatively regulate pro-liferation of RPCs. Specifically, the inactivation of Kipl in the ChxlO null mouse displays a partial recovery of retinal cell number. This rescue is incomplete so other proteins could be preventing a complete rescue. Kipl and Ink4d act in a synergistic fashion to negatively regulate proliferation so Ink4d activity in the ChxlO null mouse may be contributing to the cell number defect. Mice that are null for both ChxlO and Ink4d have been generated and the ChxlO, Ink4d double null retina shows little to no improvement over the ChxlO null retina. This suggests a lack of involvement of Ink4d in RPC proliferation in the absence of ChxlO, and may re-veal a major difference between the genetic interaction between Ink4d and Kipl with ChxlO. Billie Bixby Biology |