English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Endothelial TGF-beta signaling instructs smooth muscle cell development in the cardiac outflow tract

Boezio, G. L. M., Bensimon-Brito, A., Piesker, J., Guenther, S., Helker, C. S. M., & Stainier, D. Y. R. (2020). Endothelial TGF-beta signaling instructs smooth muscle cell development in the cardiac outflow tract. ELIFE, 9: e57603. doi:10.7554/eLife.57603.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0007-4E9B-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-4E9D-2
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Boezio, Giulia L. M.1, Author              
Bensimon-Brito, Anabela1, Author              
Piesker, Janett2, Author              
Guenther, Stefan3, Author              
Helker, Christian S. M.1, Author              
Stainier, Didier Y. R.1, Author              
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              
2Electron Microscopy, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591707              
3Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

Content

show
hide
Free keywords: -
 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-beta signaling. To better understand the role of TGF-beta signaling in OFT formation, we generated zebrafish lacking the TGF-beta 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-beta signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.

Details

show
hide
Language(s):
 Dates: 2020-09-29
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000576679100001
DOI: 10.7554/eLife.57603
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: ELIFE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 9 Sequence Number: e57603 Start / End Page: - Identifier: ISSN: 2050-084X