Dissociation of corticothalamic and thalamocortical axon targeting by an EphA7-mediated mechanism

Neuron. 2005 Nov 23;48(4):563-75. doi: 10.1016/j.neuron.2005.09.021.

Abstract

Molecular mechanisms generating the topographic organization of corticothalamic (CT) circuits, which comprise more than three-quarters of the synaptic inputs onto sensory relay neurons, and their interdependence with thalamocortical (TC) axon development are unknown. Using in utero electroporation-mediated gene transfer, we show that EphA7-mediated signaling on neocortical axons controls the within-nucleus topography of CT projections in the thalamus. Notably, CT axons that mis-express EphA7 do not shift the relative positioning of their pathway within the subcortical telencephalon (ST), indicating that they do not depend upon EphA7/ephrin-A signaling in the ST for establishing this topography. Moreover, mis-expression of cortical EphA7 results in disrupted topography of CT projections, but unchanged inter- and intra-areal topography of TC projections. Our results support a model in which EphA/ephrin-A signaling controls independently the precision with which CT and TC projections develop, yet is essential for establishing their topographic reciprocity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / physiology*
  • Brain Mapping
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology*
  • Mice
  • Mice, Inbred Strains
  • Neocortex / anatomy & histology
  • Neocortex / metabolism
  • Neural Pathways / physiology
  • Receptor, EphA5 / metabolism
  • Receptor, EphA7 / metabolism
  • Receptor, EphA7 / physiology*
  • Synaptic Transmission / physiology
  • Telencephalon / physiology
  • Thalamus / metabolism
  • Thalamus / physiology*

Substances

  • Receptor, EphA5
  • Receptor, EphA7