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

Dev Cell. 2003 Jul;5(1):45-57. doi: 10.1016/s1534-5807(03)00169-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Axons / physiology
  • COS Cells
  • Cardiovascular System / embryology*
  • Chlorocebus 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

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Lymphokines
  • Semaphorins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Neuropilin-1