Muscleblind‐like 1 is a negative regulator of TGF‐β‐dependent epithelial–mesenchymal transition of atrioventricular canal endocardial cells |
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Authors: | Natalie A. Vajda Kyle R. Brimacombe Kathryn E. LeMasters Andrea N. Ladd |
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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 |
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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. |
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Keywords: | Muscleblind‐like 1 alternative splicing transforming growth factor β epithelial– mesenchymal transition cardiac morphogenesis |
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