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PMID:12852851
| Citation |
Gu, C, Rodriguez, ER, Reimert, DV, Shu, T, Fritzsch, B, Richards, LJ, Kolodkin, AL and Ginty, DD (2003) Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev. Cell 5:45-57 |
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| Abstract |
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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| Keywords |
Amino Acid Sequence; Amino Acid Substitution; Animals; Axons/physiology; COS Cells; Cardiovascular System/embryology; Cercopithecus aethiops; Crosses, Genetic; Dendrites/physiology; Endothelial Growth Factors/metabolism; Intercellular Signaling Peptides and Proteins/metabolism; Ligands; Lymphokines/metabolism; Mice; Mice, Knockout; Mutation; Nervous System/embryology; Neuropilin-1/chemistry; Neuropilin-1/genetics; Neuropilin-1/metabolism; Protein Structure, Tertiary; Recombination, Genetic; Semaphorins/metabolism; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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