Notch3 is required for arterial identity and maturation of vascular smooth muscle cells (original) (raw)

  1. Valérie Domenga1,
  2. Peggy Fardoux1,
  3. Pierre Lacombe1,
  4. Marie Monet1,
  5. Jacqueline Maciazek1,
  6. Luke T. Krebs2,
  7. Bernard Klonjkowski3,
  8. Eliane Berrou4,
  9. Matthias Mericskay6,
  10. Zhen Li6,
  11. Elisabeth Tournier-Lasserve1,5,
  12. Thomas Gridley2, and
  13. Anne Joutel1,5,7
  14. 1INSERM E365, Faculté de Médecine Lariboisière, Paris 75010, France; 2The Jackson Laboratory, Bar Harbor, Maine 04609, USA; 3UMR1161, ENVA, INRA, AFSSA de Virologie, Maison Alfort 94704, France; 4INSERM U348 and 5Laboratoire de Cytogénétique, Hôpital Lariboisière, Paris 75010, France; 6Biologie Moléculaire de la Différenciation, Université Paris7, Paris 75251, France

Abstract

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.

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