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M. Furimsky, Y.P. Wang, V.A. Wallace; Gli3 Controls Precursor Cell Proliferation and Differentiation in the Developing Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):578.
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Purpose: Sonic hedgehog (Shh) is a secreted molecule involved in patterning the eye. In the developing retina, Shh controls cell proliferation and plays a key role in maintaining the laminar organization of the tissue. The Gli transcription factors (Gli1, Gli2 and Gli3) mediate the Shh pathway by either activating or repressing the expression of specific downstream target genes. The purpose of this study was to determine the unique and complementary roles of the Glis during retinal development. Methods: We examined the developing retinas of Gli mutant mice (in vivo and in vitro) and monitored gene expression using in situ hybridization. We also monitored cell proliferation by BrdU incorporation assay and total cell number determination. Results: The Shh signal was mediated in the retinas of all embryonic Gli mutant retinas (E14 and E18) as indicated by the expression of the target gene Gli1, and retinal morphologies were normal. In wild type retina explants, Shh promoted an increase in the number of cells expressing the retina precursor cell markers Pax6, Chx10 and Hes5 (E18 + 3 days in vitro) and rescued tissue lamination (E18 + 7 days in vitro). Gli3 mutant retinas demonstrated an overgrowth phenotype and increased expression of Cyclin D1 and Hes5. The absence of Gli3 alone was sufficient to significantly increase the total number of cells and the proportion of mitotic (BrdU+) precursor cells in retinal explants. Conclusions:Though the Glis play complementary roles in mediating Shh signaling in the embryonic retina, Gli3 is specifically required in its repressor form to control cell proliferation and differentiation post–natally.
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