SOX2 is a dose-dependent regulator of retinal neural progenitor competence

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Specification of neural progenitors in the central nervous system (CNS) and maintenance of their proliferative and differentiation capacities largely depend on the function of transcription factors. One such transcription factor, expressed in all neural progenitors of the CNS, is SOX2. We have shown that SOX2 is required for proliferation and differentiation of retinal neural progenitors. Furthermore, we have shown that lowering expression levels of SOX2 (below 40%) in mice results in restriction in retinal progenitor competence and leads to anophthalmia and microphthalmia--conditions observed in 10% of humans with haploid insufficiency in SOX2. Based on these findings we hypothesize that SOX2 functions to specify retinal neural progenitors and to maintain their proliferative and differentiation capacity during the course of retinogenesis. In this study, we will directly assess the effects of Sox2 ablation and reducing its expression levels on the properties of temporally distinct populations of retinal progenitors. [unreadable] PUBLIC HEALTH REVELANCE: We will utilize mouse genetic tools and cellular assays to dissect the molecular mechanisms affected by the expression levels of SOX2 in retinal progenitors. [unreadable] [unreadable] [unreadable]