title: Robo1 regulates semaphorin signaling to guide the migration of cortical interneurons through the ventral forebrain.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Hernández-Miranda
authors.forename: Anna
authors.initials: A
authors.lastname: Cariboni
authors.forename: Clare
authors.initials: C
authors.lastname: Faux
authors.forename: Christiana
authors.initials: C
authors.lastname: Ruhrberg
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Cho
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cloutier
authors.forename: Britta J
authors.initials: BJ
authors.lastname: Eickholt
authors.forename: John G
authors.initials: JG
authors.lastname: Parnavelas
authors.forename: William D
authors.initials: WD
authors.lastname: Andrews
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D039942:Neuropilin-1 / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D009419:Nerve Tissue Proteins; D039942:Neuropilin-1; D039943:Neuropilin-2; D011971:Receptors, Immunologic; D039961:Semaphorins; D000097905:Roundabout Proteins