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Publication : Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells.

First Author  Pérez-Martínez FJ Year  2012
Journal  Biol Open Volume  1
Issue  12 Pages  1258-63
PubMed ID  23259060 Mgi Jnum  J:192872
Mgi Id  MGI:5466761 Doi  10.1242/bio.20122816
Citation  Perez-Martinez FJ, et al. (2013) Reelin-dependent ApoER2 downregulation uncouples newborn neurons from progenitor cells. Biol Open 1(12):1258-1263
abstractText  Reelin and its receptor machinery are well known to be required for the migration and positioning of neocortical projection neurons. More recently, reelin has been shown both necessary and sufficient to determine the rate of neocortical neurogenesis. The molecular links underlying its seemingly distinct proliferative and post-proliferative functions remain unknown. Here we reveal an enriched expression of functional reelin receptors, largely of Apolipoprotein E Receptor 2 (ApoER2), in radial glia basal processes and intermediate progenitor cells during mid/late cortical development. In vivo, ApoER2 overexpression inhibits neuronal migration. In contrast, precluding excessive levels of ApoER2 in reelin-deficient cortices, by either ApoER2 knock-down or the transgenic expression of reelin in neural progenitor cells, improves neuronal migration and positioning. Our study provides groundwork for the highly orchestrated clearance of neocortical neurons from their birth site, suggesting that a reelin-dependent ApoER2 downregulation mechanism uncouples newborn neurons from progenitor cells, thereby enabling neurons to migrate.
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