title: Reelin sets the pace of neocortical neurogenesis.
abstract: Migration of neurons during cortical development is often assumed to rely on purely post-proliferative reelin signaling. However, Notch signaling, long known to regulate neural precursor formation and maintenance, is required for the effects of reelin on neuronal migration. Here, we show that reelin gain-of-function causes a higher expression of Notch target genes in radial glia and accelerates the production of both neurons and intermediate progenitor cells. Converse alterations correlate with reelin loss-of-function, consistent with reelin controlling Notch signaling during neurogenesis. Ectopic expression of reelin in isolated clones of progenitors causes a severe reduction in neuronal differentiation. In mosaic cell cultures, reelin-primed progenitor cells respond to wild-type cells by further decreasing neuronal differentiation, consistent with an increased sensitivity to lateral inhibition. These results indicate that reelin and Notch signaling cooperate to set the pace of neocortical neurogenesis, a prerequisite for proper neuronal migration and cortical layering.
authors: Instituto de Neurociencias, Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas, Campus de San Juan s/n, E-03550 San Juan de Alicante, Spain.
authors: Jarmila
authors: J
authors: Lakomá
authors: Luis
authors: L
authors: Garcia-Alonso
authors: Juan M
authors: JM
authors: Luque
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005838:Genotype; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008818:Mice, Neurologic Mutants; D018613:Microscopy, Confocal; D019579:Neocortex / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D001973:Bromodeoxyuridine