Dosage-sensitive requirement for mouse Dll4 in artery development
- António Duarte1,5,
- Masanori Hirashima3,5,6,
- Rui Benedito1,
- Alexandre Trindade1,
- Patrícia Diniz1,
- Evguenia Bekman2,
- Luís Costa1,
- Domingos Henrique2, and
- Janet Rossant3,4,7
- 1CIISA, Faculdade de Medicina Veterinária, 1300-0-477 Lisboa, Portugal; 2Instituto de Medicina Molecular, Faculdade de Medicina, 1649-9-028 Lisboa, Portugal; 3Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G1X5; 4Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8
Abstract
Involvement of the Notch signaling pathway in vascular development has been demonstrated by both gain- and loss-of-function mutations in humans, mice, and zebrafish. In zebrafish, Notch signaling is required for arterial identity by suppressing the venous fate in developing artery cells. In mice, the Notch4 receptor and the Delta-like 4 (Dll4) ligand are specifically expressed in arterial endothelial cells, suggesting a similar role. Here we show that the Dll4 ligand alone is required in a dosage-sensitive manner for normal arterial patterning in development. This implicates Dll4 as the specific mammalian endothelial ligand for autocrine endothelial Notch signaling, and suggests that Dll4 may be a suitable target for intervention in arterial angiogenesis.
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Footnotes
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1239004.
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↵5 These authors contributed equally to this work.
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↵6 Present address: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-0-8582, Japan.
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↵7 Corresponding author. E-MAIL: rossant{at}mshri.on.ca; FAX (416) 586-8588.
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- Accepted August 19, 2004.
- Received July 12, 2004.
- Cold Spring Harbor Laboratory Press
