| First Author | Chang AC | Year | 2014 |
| Journal | Dev Dyn | Volume | 243 |
| Issue | 7 | Pages | 894-905 |
| PubMed ID | 24633789 | Mgi Jnum | J:210983 |
| Mgi Id | MGI:5572995 | Doi | 10.1002/dvdy.24127 |
| Citation | Chang AC, et al. (2014) A Notch-dependent transcriptional hierarchy promotes mesenchymal transdifferentiation in the cardiac cushion. Dev Dyn 243(7):894-905 |
| abstractText | Background: Valvuloseptal defects are the most common congenital heart defects. Notch signaling-induced endothelial-to-mesenchymal transition (EMT) in the atrioventricular canal (AVC) cushions at murine embryonic day (E)9.5 is a required step during early valve development. Insights to the transcriptional network that is activated in endocardial cells (EC) during EMT and how these pathways direct valve maturation are lacking. Results: We show that at E11.5, AVC-EC retain the ability to undergo Notch-dependent EMT when explanted on collagen. EC-Notch inhibition at E10.5 blocks expression of known mesenchymal genes in E11.5 AVC-EC. To understand the genetic network and AVC development downstream of Notch signaling beyond E9.5, we constructed Tag-Seq libraries corresponding to different cell types of the E11.5 AVC and atrium in wild-type mice and in EC-Notch inhibited mice. We identified 1,400 potential Notch targets in the AVC-EC, of which 124 are transcription factors (TF). From the 124 TFs, we constructed a transcriptional hierarchy and identify 10 upstream TFs within the network. Conclusions: We validated 4 of the upstream TFs as Notch targets that are enriched in AVC-EC. Functionally, we show these 4 TFs regulate EMT in AVC explant assays. These novel signaling pathways downstream of Notch are potentially relevant to valve development. Developmental Dynamics 243:894-905, 2014. (c) 2014 Wiley Periodicals, Inc. |
