Pax6 regulation of Sox9 in the mouse retinal pigmented epithelium controls its timely differentiation and choroid vasculature development

Yamit Cohen-Tayar, Hadar Cohen, Yulia Mitiagin, Zohar Abravanel, Carmit Levy, Masha Idelson, Benjamin Reubinoff, Shalev Itzkovitz, Shaul Raviv, Klaus H. Kaestner, Pablo Blinder, Ran Elkon, Ruth Ashery-Padan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 Pax6 and Sox9 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).

Original languageEnglish
Article numberdev163691
JournalDevelopment (Cambridge)
Volume145
Issue number15
DOIs
StatePublished - Aug 2018

Funding

FundersFunder number
Israel National Center for Personalized Medicine2246/16
Israel Science Foundation-National Natural Science Foundation of China2469/16
Sackler Faculty of Medicine
Visual Disorders
United States-Israel Binational Science Foundation2013016
Israel Science Foundation228/14, 1019/15
Claire and Amédée Maratier Institute for the Study of Blindness and Visual Disorders, Tel Aviv University
Sackler Faculty of Medicine, Tel-Aviv University

    Keywords

    • Age-related macular degeneration
    • Choroid vasculature
    • Pax6
    • Retinal pigmented epithelium
    • Sox9

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