A SOX17-PDGFB signaling axis regulates aortic root development

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 () and Bin Zhou ()
Additional contact information
Pengfei Lu: Albert Einstein College of Medicine
Ping Wang: Albert Einstein College of Medicine
Bingruo Wu: Albert Einstein College of Medicine
Yidong Wang: Albert Einstein College of Medicine
Yang Liu: Albert Einstein College of Medicine
Wei Cheng: Albert Einstein College of Medicine
Xuhui Feng: Albert Einstein College of Medicine
Xinchun Yuan: Albert Einstein College of Medicine
Miriam M. Atteya: Medical University of South Carolina
Haleigh Ferro: Medical University of South Carolina
Yukiko Sugi: Medical University of South Carolina
Grant Rydquist: Cornell University
Mahdi Esmaily: Cornell University
Jonathan T. Butcher: Cornell University
Ching-Pin Chang: Albert Einstein College of Medicine
Jack Lenz: Albert Einstein College of Medicine
Deyou Zheng: Albert Einstein College of Medicine
Bin Zhou: Albert Einstein College of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31815-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31815-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31815-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().