Human disorders of cortical development: from past to present.
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.
Francis
Fiona
F
Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France. francis@cochin.inserm.fr
Meyer
Gundela
G
Fallet-Bianco
Catherine
C
Moreno
Sarah
S
Kappeler
Caroline
C
Socorro
Alfredo Cabrera
AC
Tuy
Françoise Phan Dinh
FP
Beldjord
Cherif
C
Chelly
Jamel
J
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