foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish.

Abstract:

:Vascular smooth muscle of the head derives from neural crest, but developmental mechanisms and early transcriptional drivers of the vSMC lineage are not well characterized. We find that in early development, the transcription factor foxc1b is expressed in mesenchymal cells that associate with the vascular endothelium. Using timelapse imaging, we observe that foxc1b expressing mesenchymal cells differentiate into acta2 expressing vascular mural cells. We show that in zebrafish, while foxc1b is co-expressed in acta2 positive smooth muscle cells that associate with large diameter vessels, it is not co-expressed in capillaries where pdgfrβ positive pericytes are located. In addition to being an early marker of the lineage, foxc1 is essential for vSMC differentiation; we find that foxc1 loss of function mutants have defective vSMC differentiation and that early genetic ablation of foxc1b or acta2 expressing populations blocks vSMC differentiation. Furthermore, foxc1 is expressed upstream of acta2 and is required for acta2 expression in vSMCs. Using RNA-Seq we determine an enriched intersectional gene expression profile using dual expression of foxc1b and acta2 to identify novel vSMC markers. Taken together, our data suggests that foxc1 is a marker of vSMCs and plays a critical functional role in promoting their differentiation.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Whitesell TR,Chrystal PW,Ryu JR,Munsie N,Grosse A,French CR,Workentine ML,Li R,Zhu LJ,Waskiewicz A,Lehmann OJ,Lawson ND,Childs SJ

doi

10.1016/j.ydbio.2019.06.005

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

34-47

issue

1

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(19)30209-X

journal_volume

453

pub_type

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