Class 5 transmembrane semaphorins control selective Mammalian retinal lamination and function

Neuron. 2011 Aug 11;71(3):460-73. doi: 10.1016/j.neuron.2011.06.009.


In the vertebrate retina, neurites from distinct neuronal cell types are constrained within the plexiform layers, allowing for establishment of retinal lamination. However, the mechanisms by which retinal neurites are segregated within the inner or outer plexiform layers are not known. We find that the transmembrane semaphorins Sema5A and Sema5B constrain neurites from multiple retinal neuron subtypes within the inner plexiform layer (IPL). In Sema5A⁻/⁻; Sema5B⁻/⁻ mice, retinal ganglion cells (RGCs) and amacrine and bipolar cells exhibit severe defects leading to neurite mistargeting into the outer portions of the retina. These targeting abnormalities are more prominent in the outer (OFF) layers of the IPL and result in functional defects in select RGC response properties. Sema5A and Sema5B inhibit retinal neurite outgrowth through PlexinA1 and PlexinA3 receptors both in vitro and in vivo. These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function.

Publication types

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

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Animals
  • Axons / physiology
  • Cells, Cultured
  • Dendrites / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurites / physiology*
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology
  • Photic Stimulation / methods
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology
  • Retina / growth & development
  • Retina / metabolism
  • Retina / physiology*
  • Semaphorins / genetics
  • Semaphorins / metabolism
  • Semaphorins / physiology*


  • Membrane Proteins
  • Nerve Tissue Proteins
  • Plxna1 protein, mouse
  • Plxna3 protein, mouse
  • Receptors, Cell Surface
  • Sema4d protein, mouse
  • Sema5A protein, mouse
  • Semaphorins