ZFIN ID: ZDB-PUB-170126-1
Cilia Control Vascular Mural Cell Recruitment in Vertebrates
Chen, X., Gays, D., Milia, C., Santoro, M.M.
Date: 2017
Source: Cell Reports   18: 1033-1047 (Journal)
Registered Authors: Gays, Dafne, Santoro, Massimo
Keywords: CRISPR-Cas9, blood flow, cilia, mural cells, zebrafish model
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/metabolism
  • Blood Flow Velocity
  • Cilia/metabolism*
  • Clustered Regularly Interspaced Short Palindromic Repeats/genetics
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism*
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism*
  • Hemodynamics
  • Morpholinos/genetics
  • Morpholinos/metabolism
  • Quinazolinones/pharmacology
  • RNA Interference
  • Receptors, Notch/antagonists & inhibitors
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Shear Strength
  • Signal Transduction/drug effects
  • Troponin T/antagonists & inhibitors
  • Troponin T/genetics
  • Troponin T/metabolism
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28122229 Full text @ Cell Rep.
Vascular mural cells (vMCs) are essential components of the vertebrate vascular system, controlling blood vessel maturation and homeostasis. Discrete molecular mechanisms have been associated with vMC development and differentiation. The function of hemodynamic forces in controlling vMC recruitment is unclear. Using transgenic lines marking developing vMCs in zebrafish embryos, we find that vMCs are recruited by arterial-fated vessels and that the process is flow dependent. We take advantage of tissue-specific CRISPR gene targeting to demonstrate that hemodynamic-dependent Notch activation and the ensuing arterial genetic program is driven by endothelial primary cilia. We also identify zebrafish foxc1b as a cilia-dependent Notch-specific target that is required within endothelial cells to drive vMC recruitment. In summary, we have identified a hemodynamic-dependent mechanism in the developing vasculature that controls vMC recruitment.