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Slit Promotes Branching and Elongation of Neurites of Interneurons But Not Projection Neurons from the Developing Telencephalon

Proper neuronal migration and establishment of circuitry are key processes for laying down the functional network of cortical neurons. A variety of environmental guidance cues, attractive or repulsive, have been shown to guide cell migration and axon arborization. One of these, Slit, appears to possess contrarian properties; it can either inhibit axon outgrowth or promote branching and elongation. The object of the present study was to assess the effect of Slit on MGE and neocortical neurons in culture and in the developing ventricle. When cocultured with a Slit source, E13.5 MGE explants displayed inhibited neurite outgrowth while GABA neuron dispersion away from Slit was increased. Similar inhibition of neurite outgrowth was seen in dissociated cells from E13.5 MGE, these cells were identified to be interneurons based upon their GABA staining. In contrast, E13.5 interneurons, after culture for another 5 days, were responsive to Slit by neurite branching and elongation. Projection neurons, identified by lack of GABA staining, did not respond to Slit, either by branching or elongation. Furthermore, GABA interneurons but not pyramidal neurons, appeared to avoid neocortical areas close to an implanted source of Slit in the ventricular wall. These results lead us to suggest that interneurons but not projection neurons are responsive to the chemorepellant effect of Slit. However, more mature interneurons appear to respond to Slit by neurite arborization. These results demonstrate a selective response to Slit by GABAergic neurons during neocortical development.