PUBLICATION

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

Authors
Whitesell, T.R., Chrystal, P.W., Ryu, J.R., Munsie, N., Grosse, A., French, C.R., Workentine, M.L., Li, R., Zhu, L.J., Waskiewicz, A., Lehmann, O.J., Lawson, N.D., Childs, S.J.
ID
ZDB-PUB-190615-13
Date
2019
Source
Developmental Biology   453(1): 34-47 (Journal)
Registered Authors
Childs, Sarah J., French, Curtis R., Lawson, Nathan, Lehmann, Ordan J., Waskiewicz, Andrew
Keywords
CRISPR, RNA-Seq transcriptome, Vascular smooth muscle cell, Zebrafish, acta2, foxc1b
Datasets
GEO:GSE119718
MeSH Terms
  • Animals
  • Brain/embryology
  • Brain/metabolism
  • Cell Differentiation*/genetics
  • Embryo, Nonmammalian/cytology*
  • Embryo, Nonmammalian/metabolism
  • Endothelium/metabolism
  • Forkhead Transcription Factors/metabolism*
  • Gene Expression Regulation, Developmental
  • Head/blood supply*
  • Head/embryology*
  • Mesoderm/metabolism
  • Muscle, Smooth, Vascular/cytology*
  • Myocytes, Smooth Muscle/metabolism
  • Pericytes/metabolism
  • Transcriptome/genetics
  • Up-Regulation
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/metabolism*
PubMed
31199900 Full text @ Dev. Biol.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes