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Publication : Pancreas-enriched miRNA refines endocrine cell differentiation.

First Author  Kredo-Russo S Year  2012
Journal  Development Volume  139
Issue  16 Pages  3021-31
PubMed ID  22764048 Mgi Jnum  J:187631
Mgi Id  MGI:5437569 Doi  10.1242/dev.080127
Citation  Kredo-Russo S, et al. (2012) Pancreas-enriched miRNA refines endocrine cell differentiation. Development 139(16):3021-31
abstractText  Genome-encoded microRNAs (miRNAs) provide a post-transcriptional regulatory layer that is important for pancreas development. However, how specific miRNAs are intertwined into the transcriptional network, which controls endocrine differentiation, is not well understood. Here, we show that microRNA-7 (miR-7) is specifically expressed in endocrine precursors and in mature endocrine cells. We further demonstrate that Pax6 is an important target of miR-7. miR-7 overexpression in developing pancreas explants or in transgenic mice led to Pax6 downregulation and inhibition of alpha- and beta-cell differentiation, resembling the molecular changes caused by haploinsufficient expression of Pax6. Accordingly, miR-7 knockdown resulted in Pax6 upregulation and promoted alpha- and beta-cell differentiation. Furthermore, Pax6 downregulation reversed the effect of miR-7 knockdown on insulin promoter activity. These data suggest a novel miR-7-based circuit that ensures precise control of endocrine cell differentiation.
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