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TGF-β 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-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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Abrial M,Paffett-Lugassy N,Jeffrey S,Jordan D,O'Loughlin E,Frederick CJ 3rd,Burns CG,Burns CE

doi

10.1016/j.celrep.2017.07.002

subject

Has Abstract

pub_date

2017-07-25 00:00:00

pages

973-983

issue

4

issn

2211-1247

pii

S2211-1247(17)30939-7

journal_volume

20

pub_type

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