Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments

Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14801-6. doi: 10.1073/pnas.0706919104. Epub 2007 Sep 4.

Abstract

Axons from a distinct group of neurons make contact with dendritic trees of target neurons in clearly segregated and laminated patterns, thereby forming functional units for processing multiple inputs of information in the vertebrate central nervous system. Whether and how dendrites acquire lamina-specific properties corresponding to each pathway is not known. We show here that vertebrate-specific membrane-anchored members of the UNC-6/netrin family, netrin-G1 and -G2, organize the lamina/pathway-specific differentiation of dendrites. Netrin-G1 and -G2 distribute on axons of different pathways and specifically interact with receptors NGL-1 and -2, respectively. In the hippocampus, parietal cortex, and piriform cortex, NGL-1 is concentrated in the dendritic segments corresponding to the lamina-specific termination of netrin-G1-positive axons, and NGL-2 is concentrated in distinct dendritic segments corresponding to the termination of netrin-G2-positive axons. In netrin-G1- and -G2-deficient mice, in which axonal path-finding is normal, the segmental distribution of NGL-1 and -2 is selectively disrupted, and the individual receptors are diffused along the dendrites. These findings indicate that transneuronal interactions of netrin-Gs and their specific receptors provide a molecular basis for the axonal innervation-dependent mechanism of postsynaptic membrane organization, and provide insight into the formation of the laminar structure within the dendrites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Cell Line
  • Cerebral Cortex / metabolism
  • Dendrites / metabolism*
  • Homozygote
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kidney / cytology
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Netrins
  • Protein Binding

Substances

  • Nerve Tissue Proteins
  • Netrins
  • Ntng2 protein, mouse
  • netrin-G1