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- Title
Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract.
- Authors
Boezio, Giulia L. M.; Bensimon-Brito, Anabela; Piesker, Janett; Guenther, Stefan; Helker, Christian S. M.; Stainier, Didier Y. R.
- Abstract
The development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in OFT development can lead to severe malformations, including aortic aneurysms, which are frequently associated with impaired TGF-b signaling. To better understand the role of TGF-b signaling in OFT formation, we generated zebrafish lacking the TGF-b receptor Alk5 and found a strikingly specific dilation of the OFT: alk5-/- OFTs exhibit increased EC numbers as well as extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specific alk5 overexpression in alk5-/- rescues the EC, ECM, and SMC defects. Transcriptomic analyses reveal downregulation of the ECM gene fibulin-5, which when overexpressed in ECs ameliorates OFT morphology and function. These findings reveal a new requirement for endothelial TGF-b signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.
- Subjects
SMOOTH muscle; MUSCLE growth; HEART cells; AORTIC aneurysms; EXTRACELLULAR matrix
- Publication
eLife, 2020, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.57603