miR-145 directs intestinal maturation in zebrafish

• Published in: Proceedings of the National Academy of Sciences - PNAS 2009-10, Vol.106 (42), p.17793-17798
• Main Authors: Zeng, Lei, Carter, Alyson D, Childs, Sarah J
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; 3' Untranslated Regions - physiology; Animals; Animals, Genetically Modified; Binding Sites - genetics; Biological Sciences; Danio rerio; Developmental biology; Embryos; Epithelial cells; Freshwater; GATA Transcription Factors - genetics; GATA Transcription Factors - metabolism; Gene Expression Regulation, Developmental; Green Fluorescent Proteins - genetics; Heart - embryology; In Situ Hybridization; Intestinal Mucosa - embryology; Intestinal Mucosa - metabolism; Intestines - embryology; Intestines - metabolism; Maturation; Messenger RNA; MicroRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Mimicry; Muscle, Smooth - embryology; Muscle, Smooth - metabolism; Nitric oxide; Oligonucleotides, Antisense - genetics; Phenotypes; Recombinant Proteins - genetics; Ribonucleic acid; RNA; Sensors; Smooth muscle; Three prime untranslated regions; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0903693106

The rapid specification and differentiation of the embryonic zebrafish gut is essential to provide contractility for the digestion of food. The role of microRNAs in modulating gut epithelial or smooth muscle differentiation is currently not known. Here we show that the microRNA miR-145 is strongly expressed in zebrafish gut smooth muscle and regulates its development. Modulation of miR-145 levels results in gut smooth muscle and epithelium maturation defects. Loss of miR-145 results in defects of smooth muscle function as measured by decreased nitric oxide production but also leads to increased expression of the embryonic smooth muscle markers sm22α-b, nm-mhc-b, and smoothelin. Defects in gut epithelial maturation are also present as observed by immature morphology and a complete loss of alkaline phosphatase expression. Loss or gain of miR-145 function phenocopies defects observed with altered gata6 expression and accordingly, we show that miR-145 directly represses gata6, and that gata6 is a major miR-145 target in vitro and in vivo. miR-145 therefore plays a critical role in promoting the maturation of both layers of the gut during development through regulation of gata6.