Notch3 is required for arterial identity and maturation of vascular smooth muscle cells.
Formation of a fully functional artery proceeds through a multistep process. Here we show that Notch3 is required to generate functional arteries in mice by regulating arterial differentiation and maturation of vascular smooth muscle cells (vSMC). In adult Notch3-/- mice distal arteries exhibit structural defects and arterial myogenic responses are defective. The postnatal maturation stage of vSMC is deficient in Notch3-/- mice. We further show that Notch3 is required for arterial specification of vSMC but not of endothelial cells. Our data reveal Notch3 to be the first cell-autonomous regulator of arterial differentiation and maturation of vSMC.
Domenga
Valérie
V
INSERM E365, Faculté de Médecine Lariboisière, Paris 75010, France.
Fardoux
Peggy
P
Lacombe
Pierre
P
Monet
Marie
M
Maciazek
Jacqueline
J
Krebs
Luke T
LT
Klonjkowski
Bernard
B
Berrou
Eliane
E
Mericskay
Matthias
M
Li
Zhen
Z
Tournier-Lasserve
Elisabeth
E
Gridley
Thomas
T
Joutel
Anne
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002454:Cell Differentiation; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch; D013552:Swine
D000199:Actins; D003893:Desmin; D008840:Microfilament Proteins; D009124:Muscle Proteins; C499374:NOTCH3 protein, human; C499373:Notch3 protein, mouse; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C058992:Tagln protein, mouse; C073572:Notch4 protein, mouse