ZFIN ID: ZDB-PUB-201027-17
Dual function of perivascular fibroblasts in vascular stabilization in zebrafish
Rajan, A.M., Ma, R.C., Kocha, K.M., Zhang, D.J., Huang, P.
Date: 2020
Source: PLoS Genetics   16: e1008800 (Journal)
Registered Authors: Huang, Peng, Kocha, Katrinka, Ma, Roger
Keywords: none
MeSH Terms:
  • Animals
  • Blood Vessels/growth & development
  • Blood Vessels/pathology
  • Collagen/genetics*
  • Collagen/metabolism
  • Endothelial Cells/metabolism
  • Endothelial Cells/pathology
  • Extracellular Matrix/genetics
  • Fibroblasts/cytology
  • Fibroblasts/metabolism*
  • Fibroblasts/pathology
  • Hemorrhage/genetics*
  • Hemorrhage/pathology
  • Mutant Proteins/genetics
  • Mutation/genetics
  • Myocytes, Smooth Muscle/metabolism
  • Myocytes, Smooth Muscle/pathology
  • Pericytes/metabolism*
  • Pericytes/pathology
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
PubMed: 33104690 Full text @ PLoS Genet.
Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts markedly reduces collagen deposition around endothelial cells, resulting in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors.