ZFIN ID: ZDB-PUB-201002-206
Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract
Boezio, G.L., Bensimon-Brito, A., Piesker, J., Guenther, S., Helker, C.S., Stainier, D.Y.
Date: 2020
Source: eLIFE   9: (Journal)
Registered Authors: Helker, Christian, Stainier, Didier
Keywords: Endothelium, TGF-β, cellular cross-talk, developmental biology, extracellular matrix, outflow tract, smooth muscle cells, zebrafish
Microarrays: GEO:GSE143770
MeSH Terms:
  • 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
PubMed: 32990594 Full text @ Elife
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.