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 Bioljournal_title
Developmental biologyauthors
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 SJdoi
10.1016/j.ydbio.2019.06.005subject
Has Abstractpub_date
2019-09-01 00:00:00pages
34-47issue
1eissn
0012-1606issn
1095-564Xpii
S0012-1606(19)30209-Xjournal_volume
453pub_type
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