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

• Published in: Developmental biology Vol. 453; no. 1; pp. 34 - 47
• Main Authors: Whitesell, Thomas R., Chrystal, Paul W., Ryu, Jae-Ryeon, Munsie, Nicole, Grosse, Ann, French, Curtis R., Workentine, Matthew L., Li, Rui, Zhu, Lihua Julie, Waskiewicz, Andrew, Lehmann, Ordan J., Lawson, Nathan D., Childs, Sarah J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2019
• Subjects: acta2; Animals; Brain - embryology; Brain - metabolism; Cell Differentiation - genetics; CRISPR; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Endothelium - metabolism; Forkhead Transcription Factors - metabolism; foxc1b; Gene Expression Regulation, Developmental; Head - blood supply; Head - embryology; Mesoderm - metabolism; Muscle, Smooth, Vascular - cytology; Myocytes, Smooth Muscle - metabolism; Pericytes - metabolism; RNA-Seq transcriptome; Transcriptome - genetics; Up-Regulation; Vascular smooth muscle cell; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - metabolism; CRISPR; Vascular smooth muscle cell; Zebrafish; acta2; foxc1b; RNA-Seq transcriptome
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2019.06.005

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. •Early vascular smooth muscle cells are visualized using a foxc1b transgenic line.•Foxc1b is expressed prior to the smooth muscle marker acta2.•Loss of foxc1b blocks smooth muscle cell development.•Acta2 and foxc1b double positive cells show an enriched vascular smooth muscle transcriptome.