Neogenin interacts with RGMa and netrin-1 to guide axons within the embryonic vertebrate forebrain

Dev Biol. 2006 Aug 15;296(2):485-98. doi: 10.1016/j.ydbio.2006.06.018. Epub 2006 Jun 15.


In the embryonic forebrain, pioneer axons establish a simple topography of dorsoventral and longitudinal tracts. The cues used by these axons during the initial formation of the axon scaffold remain largely unknown. We have investigated the axon guidance role of Neogenin, a member of the immunoglobulin (Ig) superfamily that binds to the chemoattractive ligand Netrin-1, as well as to the chemorepulsive ligand repulsive guidance molecule (RGMa). Here, we show strong expression of Neogenin and both of its putative ligands in the developing Xenopus forebrain. Neogenin loss-of-function mutants revealed that this receptor was essential for axon guidance in an early forming dorsoventral brain pathway. Similar mutant phenotypes were also observed following loss of either RGMa or Netrin-1. Simultaneous partial knock downs of these molecules revealed dosage-sensitive interactions and confirmed that these receptors and ligands were acting in the same pathway. The results provide the first evidence that Neogenin acts as an axon guidance molecule in vivo and support a model whereby Neogenin-expressing axons respond to a combination of attractive and repulsive cues as they navigate their ventral trajectory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • GPI-Linked Proteins
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Molecular Sequence Data
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Nerve Growth Factors / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Netrin-1
  • Neural Pathways / physiology
  • Prosencephalon / embryology*
  • Prosencephalon / metabolism
  • Prosencephalon / physiology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / physiology
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis


  • GPI-Linked Proteins
  • Ligands
  • Membrane Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Ntn1 protein, mouse
  • Rgma protein, mouse
  • Tumor Suppressor Proteins
  • Xenopus Proteins
  • neogenin
  • rgma protein, Xenopus
  • Netrin-1

Associated data

  • GENBANK/DQ173197
  • GENBANK/DQ173198