Neuropilin-1 Conveys Semaphorin and VEGF Signaling during Neural and Cardiovascular Development

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 conditio...

Full description

Saved in:
Bibliographic Details
Published in:Developmental cell 2003-07, Vol.5 (1), p.45-57
Main Authors: Gu, Chenghua, Rodriguez, E.Rene, Reimert, Dorothy V, Shu, Tianzhi, Fritzsch, Bernd, Richards, Linda J, Kolodkin, Alex L, Ginty, David D
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
Animals
Axons - physiology
Cardiovascular System - embryology
Cercopithecus aethiops
COS Cells
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
Space life sciences
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1534-5807
1878-1551
DOI:10.1016/S1534-5807(03)00169-2