MicroRNAs are essential for differentiation of the retinal pigmented epithelium and maturation of adjacent photoreceptors

Ohana, Reut and Weiman-Kelman, Benjamin and Raviv, Shaul and Tamm, Ernst R. and Pasmanik-Chor, Metsada and Rinon, Ariel and Netanely, Dvir and Shamir, Ron and Solomon, Arie S. and Ashery-Padan, Ruth (2015) MicroRNAs are essential for differentiation of the retinal pigmented epithelium and maturation of adjacent photoreceptors. DEVELOPMENT, 142 (14). 2487-+. ISSN 0950-1991, 1477-9129

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Abstract

Dysfunction of the retinal pigmented epithelium (RPE) results in degeneration of photoreceptors and vision loss and is correlated with common blinding disorders in humans. Although many proteincoding genes are known to be expressed in RPE and are important for its development and maintenance, virtually nothing is known about the in vivo roles of non-coding transcripts. The expression patterns of microRNAs (miRNAs) have been analyzed in a variety of ocular tissues, and a few were implicated to play role in RPE based on studies in cell lines. Here, through RPE-specific conditional mutagenesis of Dicer1 or Dgcr8 in mice, the importance of miRNAs for RPE differentiation was uncovered. miRNAs were found to be dispensable for maintaining RPE fate and survival, and yet they are essential for the acquisition of important RPE properties such as the expression of genes involved in the visual cycle pathway, pigmentation and cell adhesion. Importantly, miRNAs of the RPE are required for maturation of adjacent photoreceptors, specifically for the morphogenesis of the outer segments. The alterations in the miRNA and mRNA profiles in the Dicer1-deficient RPE point to a key role of miR-204 in regulation of the RPE differentiation program in vivo and uncover the importance of additional novel RPE miRNAs. This study reveals the combined regulatory activity of miRNAs that is required for RPE differentiation and for the development of the adjacent neuroretina.

Item Type: Article
Uncontrolled Keywords: TRANSCRIPTION FACTOR MITF; ADULT MAMMALIAN EYE; OUTER SEGMENT; STEM-CELLS; MOUSE EYE; MACULAR DEGENERATION; CONDITIONED MEDIUM; EXPRESSION ATLAS; APICAL MEMBRANE; VISUAL FUNCTION; RPE; Dicer1; Dgcr8; MicroRNA; Eye development; Photoreceptor; Mouse
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Jul 2019 13:14
Last Modified: 05 Jul 2019 13:14
URI: https://pred.uni-regensburg.de/id/eprint/5202

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