title: Muscleblind-like 1 is a negative regulator of TGF-beta-dependent epithelial-mesenchymal transition of atrioventricular canal endocardial cells.
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 beta-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.
authors.affiliation: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Vajda
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Brimacombe
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: LeMasters
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Ladd
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D054089:Endocardial Cushions / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D004699:Endocardium / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta