title: The inverted neurogenetic gradient of the mammalian isocortex: development and evolution.
abstract: In this paper we review recent evidence on the molecular control of cell migration in the isocortex, and present an hypothesis for the evolutionary origin of the inside-out neurogenetic gradient of this structure. We suggest that there are at least two key factors involved in the acquisition of the inside-out gradient: (i) the expression of the protein reelin, which arrests the migration of cortical plate cells by detaching them from the radial glial fiber. This permits younger neurons to use the same fiber to migrate past the previous neurons; and (ii) the second factor is an intracellular signaling pathway dependent on a cyclin-dependent protein kinase (Cdk5). Cdk5 may work by inhibiting N-cadherin mediated cell aggregation as young cells cross the cortical plate, permitting them to move to the more superficial layers. Interestingly, the mutation in Cdk5 affects the migration of only those cells belonging to superficial layers, which are considered to be an evolutionary acquisition of the mammalian isocortex.
authors.affiliation: Programa de Morfología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, 1027 Independencia Ave., PO Box 70079, Santiago 7, Chile. faboitiz@machi.med.uchile.cl
authors.forename: F
authors.initials: F
authors.lastname: Aboitiz
authors.forename: D
authors.initials: D
authors.lastname: Morales
authors.forename: J
authors.initials: J
authors.lastname: Montiel
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases; C000717127:RELN protein, human; D012697:Serine Endopeptidases