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MA Dyer, FJ Livesey, CL Cepko, G Oliver; Prox1 Regulates Progenitor Cell Proliferation and Horizontal Cell Development in the Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):830.
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During development of the retina, different cell types are generated in a characteristic order as a result of unidirectional changes in progenitor cell competence. Exit from the cell cycle must be carefully regulated during this process to ensure that the correct proportion of each cell type is generated. Relatively little is known about how cell cycle exit is coordinated with progenitor cell competence. Purpose: We set out to determine whether the Prox1 homeodomain protein, a putative cognate of Drosophila prospero, can play a role in the processes required for normal retinal development. Methods: To address this question, the expression pattern of Prox1 in the developing retina was characterized, the retinae from Prox1 deficient mice were examined, and Prox1 was overexpressed in retinal progenitor cells in vivo using a replication incompetent retrovirus. Results: Prox1 was found to be expressed during a brief period of the G2 phase of the cell cycle in mitotic progenitor cells in the embryonic mouse retina and in developing horizontal cells and AII amacrine cells during later stages (human gestational week 24 shown) View OriginalDownload SlideView OriginalDownload Slide. During the embryonic stage, Prox1 played a role in regulating the progenitors' exit from the cell cycle. Loss of Prox1 expression led to more proliferation and changes in the cell types generated including the absence of horizontal cells. Misexpression of Prox1 led to premature cell cycle exit and production of horizontal cells. Our studies also suggest that Prox1 may be involved in regulating the ability of early progenitor cells to produce their normal cohort of postmitotic daughter cells. Conclusion: Prox1 regulates embryonic retinal progenitor cell proliferation and may coordinate cell cycle exit with changes in progenitor cell competence. In addition, Prox1 is necessary and sufficient for horizontal cell fate specification. Despite their importance in visual signal processing, little was known about horizontal cell development previously.
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