| First Author | Lu P | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 4065 |
| PubMed ID | 35831318 | Mgi Jnum | J:326547 |
| Mgi Id | MGI:7313438 | Doi | 10.1038/s41467-022-31815-1 |
| Citation | Lu P, et al. (2022) A SOX17-PDGFB signaling axis regulates aortic root development. Nat Commun 13(1):4065 |
| abstractText | Developmental etiologies causing complex congenital aortic root abnormalities are unknown. Here we show that deletion of Sox17 in aortic root endothelium in mice causes underdeveloped aortic root leading to a bicuspid aortic valve due to the absence of non-coronary leaflet and mispositioned left coronary ostium. The respective defects are associated with reduced proliferation of non-coronary leaflet mesenchyme and aortic root smooth muscle derived from the second heart field cardiomyocytes. Mechanistically, SOX17 occupies a Pdgfb transcriptional enhancer to promote its transcription and Sox17 deletion inhibits the endothelial Pdgfb transcription and PDGFB growth signaling to the non-coronary leaflet mesenchyme. Restoration of PDGFB in aortic root endothelium rescues the non-coronary leaflet and left coronary ostium defects in Sox17 nulls. These data support a SOX17-PDGFB axis underlying aortic root development that is critical for aortic valve and coronary ostium patterning, thereby informing a potential shared disease mechanism for concurrent anomalous aortic valve and coronary arteries. |
