Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development

Chenghua Gu, E. Rene Rodriguez, Dorothy V. Reimert, Tianzhi Shu, Bernd Fritzsch, Linda J. Richards, Alex L. Kolodkin, David D. Ginty

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)45-57
Number of pages13
JournalDevelopmental Cell
Volume5
Issue number1
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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