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Ayumi Usui, Shinya Satoh, Minoru Tanaka, Akira Murakami, Sumiko Watanabe; Function of Transcription Factor Sox11 During Mouse Retinal Development. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6010.
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Sry-related HMG box (Sox) proteins play diverse and critical roles in a variety of morphogenetic processes during embryonic development. We focused on Sox11, which is a member of the SoxC subtype, due to its unique expression pattern revealed by our microarray analysis across different subsets of retinal progenitor cells. To elucidate the function of Sox11 in mouse retinal development, we used gain- and loss-of-function analyses.
The detailed spatial and temporal expression pattern of Sox11 in the developing mouse retina was examined by immunohistochemistry, in situ hybridization and RT-PCR. We then over-expressed Sox11 by retrovirus-mediated gene transfer in retinal explant culture prepared from E17 mouse embryos to examine its role in retinal development. In addition, we analyzed retinal cell differentiation, proliferation and survival in Sox11 knock out (Sox11-/-) mouse retina by immunohistochemistory, RT-PCR, and microarray.
Sox11 is expressed in early progenitor cells and early arising retinal neurons. The expression level of Sox11 mRNA in the retina is very high in the early stage, then decreases as development proceeds. Over-expression of Sox11 in retinal progenitor cells resulted in aberrant sub-retinal distribution of cells in explant culture. Moreover Muller glia cells failed to differentiate. The eyes of Sox11-/- mice were far smaller than those of control (WT). Proliferation and survival of Sox11-/- retinal cells were impaired in stasge-specific manner. Neurogenesis of early arising subtypes was severely suppressed at early stages. However, their differentiation overtakes WT at later developmental stages. We found that the SoxC member, Sox4 is also strongly expressed in developing mouse retina, and its expression level in retina increase as that of Sox11 subsides. Over-expression of Sox4 in retinal progenitor cells resulted in a phenotype similar to that of Sox11.
Sox11 plays roles in neurogenesis, proliferation and cell survival in retinal development and promotes differentiation of retinal neurons. The data suggest redundancy in the activities of Sox4 and Sox11, leading us to propose coordinated regulation of the retina by members of the SoxC gene family.
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