Notch3 is required for arterial identity and maturation of vascular smooth muscle cells
- Valérie Domenga1,
- Peggy Fardoux1,
- Pierre Lacombe1,
- Marie Monet1,
- Jacqueline Maciazek1,
- Luke T. Krebs2,
- Bernard Klonjkowski3,
- Eliane Berrou4,
- Matthias Mericskay6,
- Zhen Li6,
- Elisabeth Tournier-Lasserve1,5,
- Thomas Gridley2, and
- Anne Joutel1,5,7
- 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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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.308904.
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↵7 Corresponding author E-MAIL joutel{at}paris7.jussieu.fr; FAX 33-1-44-89-7755.
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- Accepted September 8, 2004.
- Received May 14, 2004.
- Cold Spring Harbor Laboratory Press
