DSCAM is a netrin receptor that collaborates with DCC in mediating turning responses to netrin-1

Cell. 2008 Jun 27;133(7):1241-54. doi: 10.1016/j.cell.2008.05.030.


During nervous system development, spinal commissural axons project toward and across the ventral midline. They are guided in part by netrin-1, made by midline cells, which attracts the axons by activating the netrin receptor DCC. However, previous studies suggest that additional receptor components are required. Here, we report that the Down's syndrome Cell Adhesion Molecule (DSCAM), a candidate gene implicated in the mental retardation phenotype of Down's syndrome, is expressed on spinal commissural axons, binds netrin-1, and is necessary for commissural axons to grow toward and across the midline. DSCAM and DCC can each mediate a turning response of these neurons to netrin-1. Similarly, Xenopus spinal neurons exogenously expressing DSCAM can be attracted by netrin-1 independently of DCC. These results show that DSCAM is a receptor that can mediate turning responses to netrin-1 and support a key role for netrin/DSCAM signaling in commissural axon guidance in vertebrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • Embryo, Mammalian / metabolism
  • In Vitro Techniques
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Nerve Growth Factors / metabolism*
  • Netrin Receptors
  • Netrin-1
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Cell Surface / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Spinal Cord / metabolism
  • Tumor Suppressor Proteins / metabolism*
  • Xenopus


  • Membrane Proteins
  • Nerve Growth Factors
  • Netrin Receptors
  • Ntn1 protein, rat
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Netrin-1