title: Connexin45 regulates endothelial-induced mesenchymal cell differentiation toward a mural cell phenotype.
abstract: OBJECTIVE
  The focus of this study was to investigate the role of connexin (Cx) 45 in endothelial-induced mural cell differentiation.
  
  
  RESULTS
  We created mural cell precursors that stably express only Cx45 in Cx43-deficient mesenchymal cells (ReCx45), and used our in vitro model of blood vessel assembly to assess the capacity of this Cx to support endothelial-induced mural cell differentiation. Lucifer Yellow dye injection and dual whole-cell patch clamping revealed that functional gap junctions exhibiting properties of Cx45-containing channels formed among ReCx45 transfectants, and between ReCx45 and endothelial cells. Heterocellular Cx45-containing gap junction channels enabled transforming growth factor-β activation and promoted the upregulation of mural cell-specific proteins in the mesenchymal precursors.
  
  
  CONCLUSIONS
  These studies reveal a critical role for Cx45 in the regulation of endothelial-induced mural cell differentiation, which is consistent with the phenotype of Cx45-deficient embryos that exhibit dysregulated transforming growth factor-β and lack mural cell development.
authors.affiliation: Yale Cardiovascular Research Center, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Fang
authors.forename: Cuiping
authors.initials: C
authors.lastname: Dai
authors.forename: David T
authors.initials: DT
authors.lastname: Kurjiaka
authors.forename: Janis M
authors.initials: JM
authors.lastname: Burt
authors.forename: Karen K
authors.initials: KK
authors.lastname: Hirschi
mesh_terms: D000818:Animals; D002417:Cattle; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D005838:Genotype; D007546:Isoquinolines / Q000378:metabolism; D008564:Membrane Potentials; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000378:metabolism*; D010641:Phenotype; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D017630:Connexins; D005456:Fluorescent Dyes; D007546:Isoquinolines; D016212:Transforming Growth Factor beta; C082920:connexin 45; C017475:lucifer yellow