PUBLICATION
TGF-β Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation
- Authors
- Abrial, M., Paffett-Lugassy, N., Jeffrey, S., Jordan, D., O'Loughlin, E., Frederick, C.J., Burns, C.G., Burns, C.E.
- ID
- ZDB-PUB-170727-1
- Date
- 2017
- Source
- Cell Reports 20: 973-983 (Journal)
- Registered Authors
- Burns (Erter), Caroline, Burns, Geoff, Paffett-Lugassy, Noelle
- Keywords
- Smad, TGF-β, cardiovascular, great vessels, nkx2.5, pharyngeal arch artery, small-molecule screen, zebrafish
- MeSH Terms
-
- Animals
- Arteries/cytology*
- Branchial Region/blood supply*
- Homeobox Protein Nkx-2.5/genetics
- Homeobox Protein Nkx-2.5/metabolism
- Signal Transduction
- Transforming Growth Factor beta/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 28746880 Full text @ Cell Rep.
Citation
Abrial, M., Paffett-Lugassy, N., Jeffrey, S., Jordan, D., O'Loughlin, E., Frederick, C.J., Burns, C.G., Burns, C.E. (2017) TGF-β Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation. Cell Reports. 20:973-983.
Abstract
The pharyngeal arch arteries (PAAs) are transient embryonic blood vessels that mature into critical segments of the aortic arch and its branches. Although defects in PAA development cause life-threating congenital cardiovascular defects, the molecular mechanisms that orchestrate PAA morphogenesis remain unclear. Through small-molecule screening in zebrafish, we identified TGF-β signaling as indispensable for PAA development. Specifically, chemical inhibition of the TGF-β type I receptor ALK5 impairs PAA development because nkx2.5+ PAA progenitor cells fail to differentiate into tie1+ angioblasts. Consistent with this observation, we documented a burst of ALK5-mediated Smad3 phosphorylation within PAA progenitors that foreshadows angioblast emergence. Remarkably, premature induction of TGF-β receptor activity stimulates precocious angioblast differentiation, thereby demonstrating the sufficiency of this pathway for initiating the PAA progenitor to angioblast transition. More broadly, these data uncover TGF-β as a rare signaling pathway that is necessary and sufficient for angioblast lineage commitment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping