title: Cilia Control Vascular Mural Cell Recruitment in Vertebrates.
abstract: 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.
authors.affiliation: Vesalius Research Center, VIB-KUL, Leuven 3000, Belgium.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin 10126, Italy.
authors.forename: Dafne
authors.initials: D
authors.lastname: Gays
authors.affiliation: Vesalius Research Center, VIB-KUL, Leuven 3000, Belgium.
authors.forename: Carlo
authors.initials: C
authors.lastname: Milia
authors.affiliation: Vesalius Research Center, VIB-KUL, Leuven 3000, Belgium; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin 10126, Italy. Electronic address: massimo.santoro@kuleuven.vib.be.
authors.forename: Massimo M
authors.initials: MM
authors.lastname: Santoro
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D001783:Blood Flow Velocity; D002923:Cilia / Q000378:metabolism*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006439:Hemodynamics; D060172:Morpholinos / Q000235:genetics / Q000378:metabolism; D052999:Quinazolinones / Q000494:pharmacology; D034622:RNA Interference; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D033081:Shear Strength; D015398:Signal Transduction / Q000187:drug effects; D020107:Troponin T / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C426858:Foxc1b protein, zebrafish; D060172:Morpholinos; D052999:Quinazolinones; D051880:Receptors, Notch; D020107:Troponin T; D029961:Zebrafish Proteins; C000595851:ciliobrevin D; C480681:tnnt2a protein, zebrafish
keywords: CRISPR-Cas9; blood flow; cilia; mural cells; zebrafish model