Journal
JOURNAL OF NEUROSCIENCE
Volume 31, Issue 16, Pages 6174-6187Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5464-10.2011
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Funding
- Wellcome Trust [074549, 089775]
- Mexican Council for Science and Technology (Consejo Nacional de Ciencia y Tecnologia)
- Canadian Institutes of Health Research, Centre of Excellence in Commercialization and Research of the Montreal Neurological Institute
- Le Fonds de la Recherche en Sante de Quebec
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Cortical interneurons, generated predominantly in the medial ganglionic eminence, migrate around and avoid the developing striatum in the subpallium en route to the cortex. This is attributable to the chemorepulsive cues of class 3 semaphorins expressed in the striatal mantle and acting through neuropilin (Nrp1 and Nrp2) receptors expressed in these cells. Cortical interneurons also express Robo receptors, and we show here that in mice lacking Robo1, but not Robo2, these cells migrate aberrantly through the striatum. In vitro experiments demonstrated that interneurons lacking Robo1 function are significantly less responsive to the effects of semaphorins. Failure to respond to semaphorin appears to be attributable to a reduction in Nrp1 and PlexinA1 receptors within these cells. Biochemical studies further demonstrated that Robo1 binds directly to Nrp1, but not to semaphorins, and this interaction is mediated by a region contained within its first two Ig domains. Thus, we show for the first time that Robo1 interacts with Nrp1 to modulate semaphorin signaling in the developing forebrain and direct the migration of interneurons through the subpallium and into the cortex.
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