Article

Reelin Together with ApoER2 Regulates Interneuron Migration in the Olfactory Bulb

Institute of Anatomy and Cell Biology I, University of Freiburg, Freiburg, Germany.
PLoS ONE (Impact Factor: 3.23). 11/2012; 7(11):e50646. DOI: 10.1371/journal.pone.0050646
Source: PubMed

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.

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    • "Conversely, Reelin produced by these cells is required for interneurons to detach from the RMS and adopt their normal laminar position (Hack et al., 2002; Hellwig et al., 2012). In reeler mutants, for example, some TH + and CB + interneurons fail to reach the glomerular layer and instead reside in the external plexiform layer; some defects have also been reported in the distribution of CR + interneurons in the granular layer (Hellwig et al., 2012). Nevertheless, the position of PV + interneurons in the external plexiform layer, and most periglomerular interneurons, is unaffected by the loss of Reelin signaling, which suggests that the correct laminar distribution of olfactory bulb interneurons depends on additional factors . "
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