Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain.
Newborn cerebral cortical neurons migrate along radial glia to the cortical plate. Experiments using a collagen gel assay revealed that the choroid plexus repelled cerebral cortical neurons and olfactory interneuron precursors, which were mimicked by Neuro-2A cells. Fractionation of Neuro-2A-conditioned medium identified a protein of 190 kDa, equivalent to full-length Slit proteins. Indeed, it cross-reacted with an antibody against Slit2, suggesting that it is either Slit2 or another Slit protein. Further, Slit2, expressed in COS cells, repelled cerebral cortical neurons and olfactory interneuron precursors. Thus, Slit2, which is expressed by the choroid plexus and the septum, acts as a chemorepulsive factor for neuronal migration. These results suggest chemorepulsion as a guidance mechanism for neuronal migration in the developing forebrain.
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Rammelkamp Center for Education and Research, MetroHealth Medical Center, Cleveland, Ohio 44109, USA. hhu@research.mhmc.org
D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity; D015153:Blotting, Western; D019556:COS Cells; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D002831:Choroid Plexus / Q000254:growth & development / Q000648:ultrastructure; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007395:Interneurons / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000502:physiology; D000098552:Slit Homolog 2 Protein
D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000098552:Slit Homolog 2 Protein