title: Reelin together with ApoER2 regulates interneuron migration in the olfactory bulb.
abstract: One pathway regulating the migration of neurons during development of the mammalian cortex involves the extracellular matrix protein Reelin. Reelin and components of its signaling cascade, the lipoprotein receptors ApoER2 and Vldlr and the intracellular adapter protein Dab1 are pivotal for a correct layer formation during corticogenesis. The olfactory bulb (OB) as a phylogenetically old cortical region is known to be a prominent site of Reelin expression. Although some aspects of Reelin function in the OB have been described, the influence of Reelin on OB layer formation has so far been poorly analyzed. Here we studied animals deficient for either Reelin, Vldlr, ApoER2 or Dab1 as well as double-null mutants. We performed organotypic migration assays, immunohistochemical marker analysis and BrdU incorporation studies to elucidate roles for the different components of the Reelin signaling cascade in OB neuroblast migration and layer formation. We identified ApoER2 as being the main receptor responsible for Reelin mediated detachment of neuroblasts and correct migration of early generated interneurons within the OB, a prerequisite for correct OB lamination.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Freiburg, Germany. sabine.hellwig@uniklinik-freiburg.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
authors.forename: Iris
authors.initials: I
authors.lastname: Hack
authors.forename: Birgit
authors.initials: B
authors.lastname: Zucker
authors.forename: Bianka
authors.initials: B
authors.lastname: Brunne
authors.forename: Dirk
authors.initials: D
authors.lastname: Junghans
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases