title: Human disorders of cortical development: from past to present.
abstract: Epilepsy and mental retardation, originally of unknown cause, are now known to result from many defects including cortical malformations, neuronal circuitry disorders and perturbations of neuronal communication and synapse function. Genetic approaches in combination with MRI and related imaging techniques continually allow a re-evaluation and better classification of these disorders. Here we review our current understanding of some of the primary defects involved, with insight from recent molecular biology advances, the study of mouse models and the results of neuropathology analyses. Through these studies the molecular determinants involved in the control of neuron number, neuronal migration, generation of cortical laminations and convolutions, integrity of the basement membrane at the pial surface, and the establishment of neuronal circuitry are being elucidated. We have attempted to integrate these results with the available data concerning, in particular, human brain development, and to emphasize the limitations in some cases of extrapolating from rodent models. Taking such species differences into account is clearly critical for understanding the pathophysiological mechanisms associated with these disorders.
authors.affiliation: Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France. francis@cochin.inserm.fr
authors.forename: Fiona
authors.initials: F
authors.lastname: Francis
authors.forename: Gundela
authors.initials: G
authors.lastname: Meyer
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallet-Bianco
authors.forename: Sarah
authors.initials: S
authors.lastname: Moreno
authors.forename: Caroline
authors.initials: C
authors.lastname: Kappeler
authors.forename: Alfredo Cabrera
authors.initials: AC
authors.lastname: Socorro
authors.forename: Françoise Phan Dinh
authors.initials: FP
authors.lastname: Tuy
authors.forename: Cherif
authors.initials: C
authors.lastname: Beldjord
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000235:genetics / Q000266:history / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000002:abnormalities / Q000254:growth & development / Q000473:pathology; D049669:History, 16th Century; D049670:History, 17th Century; D049673:History, 20th Century; D049674:History, 21st Century; D049690:History, Ancient; D006801:Humans; D009154:Mutation