Dissociation of corticothalamic and thalamocortical axon targeting by an EphA7-mediated mechanism.
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.
Torii
Masaaki
M
Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37203, USA.
Levitt
Pat
P
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D019579:Neocortex / Q000033:anatomy & histology / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D036123:Receptor, EphA5 / Q000378:metabolism; D036141:Receptor, EphA7 / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013687:Telencephalon / Q000502:physiology; D013788:Thalamus / Q000378:metabolism / Q000502:physiology*
D036123:Receptor, EphA5; D036141:Receptor, EphA7