Muscleblind-like 1 is a negative regulator of TGF-beta-dependent epithelial-mesenchymal transition of atrioventricular canal endocardial cells.
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.
Vajda
Natalie A
NA
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Brimacombe
Kyle R
KR
LeMasters
Kathryn E
KE
Ladd
Andrea N
AN
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*
D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta