Journal
DEVELOPMENTAL CELL
Volume 5, Issue 1, Pages 45-57Publisher
CELL PRESS
DOI: 10.1016/S1534-5807(03)00169-2
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Funding
- NHLBI NIH HHS [P01 HL070295, P01-HL70295] Funding Source: Medline
- NIDCD NIH HHS [R01 DC005590-02, R01 DC005590, R01-DC 005590] Funding Source: Medline
- NIMH NIH HHS [R01 MH059199, R01MH59199] Funding Source: Medline
- NINDS NIH HHS [F32 NS011016, 5F32NS11016] Funding Source: Medline
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Neuropilin-1 (Npn-1) is a receptor that binds multiple ligands from structurally distinct families, including secreted semaphorins (Sema) and vascular endothelial growth factors (VEGF). We generated npn-1 knockin mice, which express an altered ligand binding site variant of Npn-1, and npn-1 conditional null mice to establish the cell-type- and ligand specificity of Npn-1 function in the developing cardiovascular and nervous systems. Our results show that VEGF-Npn-1 signaling in endothelial cells is required for angiogenesis. In striking contrast, Sema-Npn-1 signaling is not essential for general vascular development but is required for axonal pathfinding by several populations of neurons in the CNS and PNS. Remarkably, both Sema-Npn-1 signaling and VEGF-Npn-1 signaling are critical for heart development. Therefore, Npn-1 is a multifunctional receptor that mediates the activities of structurally distinct ligands during development of the heart, vasculature, and nervous system.
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