title: Differentiation of vascular smooth muscle cells from local precursors during embryonic and adult arteriogenesis requires Notch signaling.
abstract: Vascular smooth muscle cells (VSMC) have been suggested to arise from various developmental sources during embryogenesis, depending on the vascular bed. However, evidence also points to a common subpopulation of vascular progenitor cells predisposed to VSMC fate in the embryo. In the present study, we use binary transgenic reporter mice to identify a Tie1(+)CD31(dim)vascular endothelial (VE)-cadherin(-)CD45(-) precursor that gives rise to VSMC in vivo in all vascular beds examined. This precursor does not represent a mature endothelial cell, because a VE-cadherin promoter-driven reporter shows no expression in VSMC during murine development. Blockade of Notch signaling in the Tie1(+) precursor cell, but not the VE-cadherin(+) endothelial cell, decreases VSMC investment of developing arteries, leading to localized hemorrhage in the embryo at the time of vascular maturation. However, Notch signaling is not required in the Tie1(+) precursor after establishment of a stable artery. Thus, Notch activity is required in the differentiation of a Tie1(+) local precursor to VSMC in a spatiotemporal fashion across all vascular beds.
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3.
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Michela
authors.initials: M
authors.lastname: Noseda
authors.forename: Michelle
authors.initials: M
authors.lastname: Higginson
authors.forename: Michelle
authors.initials: M
authors.lastname: Ly
authors.forename: Alexandre
authors.initials: A
authors.lastname: Patenaude
authors.forename: Megan
authors.initials: M
authors.lastname: Fuller
authors.forename: Alastair H
authors.initials: AH
authors.lastname: Kyle
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Minchinton
authors.forename: Mira C
authors.initials: MC
authors.lastname: Puri
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dumont
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001158:Arteries / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D001483:Base Sequence; D015820:Cadherins / Q000172:deficiency / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017493:Leukocyte Common Antigens / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D032390:Myoblasts, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D042810:Receptor, TIE-1 / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D017931:DNA Primers; D017493:Leukocyte Common Antigens; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042810:Receptor, TIE-1; D051880:Receptors, Notch; D000099152:Cadherin 5; C516770:Ptprc protein, mouse