title: Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos.
abstract: Atrioventricular (AV) cushions are the precursors of AV septum and valves. In this study, we examined roles of Smad4 during AV cushion development using a conditional gene inactivation approach. We found that endothelial/endocardial inactivation of Smad4 led to the hypocellular AV cushion defect and that both reduced cell proliferation and increased apoptosis contributed to the defect. Expression of multiple genes critical for cushion development was down-regulated in mutant embryos. In collagen gel assays, the number of mesenchymal cells formed is significantly reduced in mutant AV explants compared to that in control explants, suggesting that the reduction of cushion mesenchyme formation in mutants is unlikely secondary to their gross vasculature abnormalities. Using a previously developed immortal endocardial cell line, we showed that Smad4 is required for BMP signaling- stimulated upregulation of Tbx20 and Gata4. Therefore, our data collectively support the cell-autonomous requirement of endocardial Smad4 in regulating AV cushion development.
authors.affiliation: Research Division, Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Langying
authors.initials: L
authors.lastname: Song
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Bingruo
authors.initials: B
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Jiao
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D054089:Endocardial Cushions / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004699:Endocardium / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice / Q000196:embryology* / Q000235:genetics; D008822:Mice, Transgenic; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051901:Smad4 Protein; C490810:Smad4 protein, mouse