|ZFIN ID: ZDB-PUB-170727-1|
TGF-β Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation
Abrial, M., Paffett-Lugassy, N., Jeffrey, S., Jordan, D., O'Loughlin, E., Frederick, C.J., Burns, C.G., Burns, C.E.
|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|
|PubMed:||28746880 Full text @ Cell Rep.|
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.
ABSTRACTThe 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.