Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing

Neuron. 2012 May 24;74(4):676-90. doi: 10.1016/j.neuron.2012.03.025.


At the optic chiasm, retinal ganglion cells (RGCs) project ipsi- or contralaterally to establish the circuitry for binocular vision. Ipsilateral guidance programs have been characterized, but contralateral guidance programs are not well understood. Here, we identify a tripartite molecular system for contralateral RGC projections: Semaphorin6D (Sema6D) and Nr-CAM are expressed on midline radial glia and Plexin-A1 on chiasm neurons, and Plexin-A1 and Nr-CAM are also expressed on contralateral RGCs. Sema6D is repulsive to contralateral RGCs, but Sema6D in combination with Nr-CAM and Plexin-A1 converts repulsion to growth promotion. Nr-CAM functions as a receptor for Sema6D. Sema6D, Plexin-A1, and Nr-CAM are all required for efficient RGC decussation at the optic chiasm. These findings suggest a mechanism by which a complex of Sema6D, Nr-CAM, and Plexin-A1 at the chiasm midline alters the sign of Sema6D and signals Nr-CAM/Plexin-A1 receptors on RGCs to implement the contralateral RGC projection.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism*
  • Optic Chiasm / cytology
  • Optic Chiasm / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Retina / cytology
  • Retina / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism*
  • Semaphorins / metabolism*


  • Cell Adhesion Molecules
  • Nerve Tissue Proteins
  • Nrcam protein, mouse
  • Plxna1 protein, mouse
  • Receptors, Cell Surface
  • Sema6d protein, mouse
  • Semaphorins