Abstract
The thalamocortical tract carries sensory information to the neocortex. It has long been recognized that the neocortical pioneer axons of subplate neurons are essential for thalamocortical development. Herein we report that an axon guidance cue, draxin, is expressed in early-born neocortical neurons, including subplate neurons, and is necessary for thalamocortical development. In draxin−/− mice, thalamocortical axons do not enter the neocortex. This phenotype is sufficiently rescued by the transgenic expression of draxin in neocortical neurons. Genetic interaction data suggest that draxin acts through Deleted in colorectal cancer (DCC) and Neogenin (Neo1), to regulate thalamocortical projections in vivo. Draxin promotes the outgrowth of thalamic axons in vitro and this effect is abolished in thalamic neurons from Dcc and Neo1 double mutants. These results suggest that draxin from neocortical neurons controls thalamocortical projections into the neocortex, and that this effect is mediated through the DCC and Neo1 receptors.
Highlights
The thalamocortical tract carries sensory information to the neocortex
In draxin À / À mice, the number of NF-positive axons increased in the external capsule (Fig. 1a, arrowheads), while the thickness of axon bundles reduced in the internal capsule (Fig. 1a, arrow)
We observed that some of the TAG-1-positive axons in draxin À / À mice entered the internal capsule and reached the thalamus (Supplementary Fig. 1a, arrowhead). These results suggest that draxin is required for the normal guidance of corticofugal axons from the neocortex to the internal capsule
Summary
The thalamocortical tract carries sensory information to the neocortex. It has long been recognized that the neocortical pioneer axons of subplate neurons are essential for thalamocortical development. Corticothalamic and thalamocortical axons concurrently grow into the subcortical telencephalon, where they meet to form the internal capsule and continue to extend in opposite directions to reach their targets[1] It has been known for over two decades that the guidance of thalamocortical projections is dependent on the neocortical subplate neurons, which pioneer the corticofugal pathway from the neocortex to the internal capsule[2,3,4]. We showed that draxin promotes the axonal growth of thalamic neurons in vitro, which was absent in thalamic neurons from Neo1Gt/Gt;Dcc À / À embryos These results suggest that draxin from neocortical neurons controls the guidance of thalamocortical projections and this effect of draxin is mediated through the DCC and Neo[1] receptors
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