RRC ID 66027
Author Boezio GL, Bensimon-Brito A, Piesker J, Guenther S, Helker CS, Stainier DY.
Title Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract.
Journal Elife
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-β signaling. To better understand the role of TGF-β signaling in OFT formation, we generated zebrafish lacking the TGF-β 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-β signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.
Volume 9
Published 2020-9-29
DOI 10.7554/eLife.57603
PII 57603
PMID 32990594
PMC PMC7524555
MeSH Animals Aorta / cytology Aorta / metabolism Endothelium, Vascular / cytology Endothelium, Vascular / metabolism* Heart Ventricles / cytology Heart Ventricles / metabolism Myocytes, Smooth Muscle / metabolism* Receptor, Transforming Growth Factor-beta Type I / metabolism Smad3 Protein / metabolism Transforming Growth Factor beta / metabolism* Zebrafish Zebrafish Proteins / metabolism
IF 7.08
Zebrafish TgBAC(pdgfrb:EGFP)ncv22Tg