Pax6 regulation of in the mouse retinal pigmented epithelium controls its timely differentiation and choroid vasculature development.

Development 2018 08 9;145(15). Epub 2018 Aug 9.

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neurosciences, Tel Aviv University, Tel Aviv 69978, Israel

The synchronized differentiation of neuronal and vascular tissues is crucial for normal organ development and function, although there is limited information about the mechanisms regulating the coordinated development of these tissues. The choroid vasculature of the eye serves as the main blood supply to the metabolically active photoreceptors, and develops together with the retinal pigmented epithelium (RPE). Here, we describe a novel regulatory relationship between the RPE transcription factors Pax6 and Sox9 that controls the timing of RPE differentiation and the adjacent choroid maturation. We used a novel machine learning algorithm tool to analyze high resolution imaging of the choroid in and conditional mutant mice. Additional unbiased transcriptomic analyses in mutant mice and RPE cells generated from human embryonic stem cells, as well as chromatin immunoprecipitation and high-throughput analyses, revealed secreted factors that are regulated by Pax6 and Sox9. These factors might be involved in choroid development and in the pathogenesis of the common blinding disease: age-related macular degeneration (AMD).

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Source
http://dev.biologists.org/lookup/doi/10.1242/dev.163691
Publisher Site
http://dx.doi.org/10.1242/dev.163691DOI Listing
August 2018

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