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Publication : Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos.

First Author  Song L Year  2011
Journal  Dev Dyn Volume  240
Issue  1 Pages  211-20
PubMed ID  21089072 Mgi Jnum  J:167617
Mgi Id  MGI:4868645 Doi  10.1002/dvdy.22493
Citation  Song L, et al. (2011) Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos. Dev Dyn 240(1):211-20
abstractText  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.
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