A SOX17-PDGFB signaling axis regulates aortic root development

• DOI: 10.1038/s41467-022-31815-1
• Publication Date: 2022-07-13T22:05:04Z
• Authors: Pengfei Lu; Ping Wang; Bingruo Wu; Yidong Wang; Yang Liu; Wei Cheng; Xuhui Feng; Xinchun Yuan; Miriam M. Atteya; Haleigh Ferro; Yukiko Sugi; Grant Rydquist; Mahdi Esmaily; Jonathan T. Butcher; Ching-Pin Chang; Jack Lenz; Deyou Zheng; Bin Zhou
• Keywords: PDGFB

Abstract Developmental etiologies causing complex congenital aortic root abnormalities are unknown. Here we show that deletion of Sox17 in endothelium mice causes underdeveloped leading to a bicuspid valve due the absence non-coronary leaflet and mispositioned left coronary ostium. The respective defects associated with reduced proliferation mesenchyme smooth muscle derived from second heart field cardiomyocytes. Mechanistically, SOX17 occupies Pdgfb transcriptional enhancer promote its transcription inhibits endothelial PDGFB growth signaling mesenchyme. Restoration rescues ostium nulls. These data support SOX17-PDGFB axis underlying development is critical for patterning, thereby informing potential shared disease mechanism concurrent anomalous arteries.