Title

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

UMMS Affiliation

Department of Molecular, Cell, and Cancer Biology; Program in Molecular Medicine

Publication Date

2019-06-11

Document Type

Article

Disciplines

Cell Biology | Developmental Biology | Musculoskeletal System

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 pdgfrbeta 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.

Keywords

CRISPR, RNA-Seq transcriptome, Vascular smooth muscle cell, Zebrafish, acta2, foxc1b

DOI of Published Version

10.1016/j.ydbio.2019.06.005

Source

Dev Biol. 2019 Jun 11. pii: S0012-1606(19)30209-X. doi: 10.1016/j.ydbio.2019.06.005. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Developmental biology

Related Resources

Link to Article in PubMed

PubMed ID

31199900

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