PUBLICATION
Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract
- Authors
- Boezio, G.L., Bensimon-Brito, A., Piesker, J., Guenther, S., Helker, C.S., Stainier, D.Y.
- ID
- ZDB-PUB-201002-206
- Date
- 2020
- Source
- eLIFE 9: (Journal)
- Registered Authors
- Bensimon-Brito, Anabela, Helker, Christian, Stainier, Didier
- Keywords
- Endothelium, TGF-β, cellular cross-talk, developmental biology, extracellular matrix, outflow tract, smooth muscle cells, zebrafish
- Datasets
- 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
Citation
Boezio, G.L., Bensimon-Brito, A., Piesker, J., Guenther, S., Helker, C.S., Stainier, D.Y. (2020) Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract. eLIFE. 9:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping