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Development. 2015 Jul 15;142(14):2487-98. doi: 10.1242/dev.121533. Epub 2015 Jun 10.

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

Author information

1
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
2
Institute of Human Anatomy and Embryology, University of Regensburg, D-93053 Regensburg, Germany.
3
Bioinformatics Unit, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
4
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel.
5
The Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University Sheba Medical Center, Tel Hashomer 52621, Israel.
6
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel ruthash@post.tau.ac.il.

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 protein-coding 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.

KEYWORDS:

Dgcr8; Dicer1; Eye development; MicroRNA; Mouse; Photoreceptor; RPE

PMID:
26062936
DOI:
10.1242/dev.121533
[Indexed for MEDLINE]
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