TGF-? Signaling Is Necessary and Sufficient for Pharyngeal Arch Artery Angioblast Formation.

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-? signaling as indispensable for PAA development. Specifically, chemical inhibition of the TGF-? 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-? 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-? as a rare signaling pathway that is necessary and sufficient for angioblast lineage commitment.

SUBMITTER: Abrial M 

PROVIDER: S-EPMC5565225 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature