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Muscleblind‐like 1 is a negative regulator of TGF‐β‐dependent epithelial–mesenchymal transition of atrioventricular canal endocardial cells
Authors:Natalie A. Vajda  Kyle R. Brimacombe  Kathryn E. LeMasters  Andrea N. Ladd
Affiliation:1. Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio;2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
Abstract:
The development of the valves and septa of the heart depends on the formation and remodeling of endocardial cushions. Here, we report that the alternative splicing regulator muscleblind‐like 1 (MBNL1) exhibits a regionally restricted pattern of expression in canal region endocardium and ventricular myocardium during endocardial cushion development in chicken. Knockdown of MBNL1 in atrioventricular explants leads to a transforming growth factor β‐dependent increase in epithelial–mesenchymal transition (EMT) of endocardial cells. This reveals a novel role for MBNL1 during embryonic development, and represents the first evidence that an alternative splicing regulator is a key player in endocardial cushion development. Developmental Dynamics 238:3266–3272, 2009. © 2009 Wiley‐Liss, Inc.
Keywords:Muscleblind‐like 1  alternative splicing  transforming growth factor β    epithelial–  mesenchymal transition  cardiac morphogenesis
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