Abstract
AbstractNormal vision depends on the retinal pigmented epithelium (RPE), a metabolic cell layer that is vital to the development and function of the adjacent retinal photoreceptors. The aim of this study was to uncover the transcriptional regulatory program and the cis‐regulatory elements required for RPE differentiation and maintenance. Lhx2 is a member of LIM homeodomain (LIM‐HD) protein family; it is a key factor for neural differentiation and is known to be required for early morphogenesis and patterning of the vertebrate eye. To discover the roles of Lhx2 in the differentiation of the mammalian RPE, we conducted functional studies in vivo using conditional mutagenesis in mouse, and knockdown in human RPE derived from embryonic stem cells (hES‐RPE). This was combined with global identification of regulatory regions bound by Lhx2 and a genomic characterization of these sites in the course of RPE differentiation. The results place Lhx2 upstream of a complex regulatory network that controls RPE differentiation, morphology and function in mice and humans.
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