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Human disorders of cortical development: from past to present

Authors

  • Fiona Francis,

    1. Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France
    2. INSERM U567, Paris, France
    3. CNRS UMR 8104, Paris, France
    4. Université René Descartes, Paris V, 75014 Paris, France
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    • *

      F.F. and G.M. contributed equally to this review

  • Gundela Meyer,

    1. Department of Anatomy, Faculty of Medicine, University of La Laguna, La Laguna 39071, Tenerife, Spain
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    • *

      F.F. and G.M. contributed equally to this review

  • Catherine Fallet-Bianco,

    1. Service d'Anatomie Pathologique, Hôpital Sainte Anne, 1, rue Cabanis, 75014 Paris, France
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  • Sarah Moreno,

    1. Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France
    2. INSERM U567, Paris, France
    3. CNRS UMR 8104, Paris, France
    4. Université René Descartes, Paris V, 75014 Paris, France
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  • Caroline Kappeler,

    1. Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France
    2. INSERM U567, Paris, France
    3. CNRS UMR 8104, Paris, France
    4. Université René Descartes, Paris V, 75014 Paris, France
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  • Alfredo Cabrera Socorro,

    1. Department of Anatomy, Faculty of Medicine, University of La Laguna, La Laguna 39071, Tenerife, Spain
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  • Françoise Phan Dinh Tuy,

    1. Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France
    2. INSERM U567, Paris, France
    3. CNRS UMR 8104, Paris, France
    4. Université René Descartes, Paris V, 75014 Paris, France
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  • Cherif Beldjord,

    1. Laboratory of Biochemical Genetics, CHU Cochin-Port-Royal, 75014 Paris, France
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  • Jamel Chelly

    1. Institut Cochin, Département de Génétique et Développement, Paris, F-75014 France
    2. INSERM U567, Paris, France
    3. CNRS UMR 8104, Paris, France
    4. Université René Descartes, Paris V, 75014 Paris, France
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Dr F. Francis, Institut Cochin – CHU Cochin, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
E-mail: francis@cochin.inserm.fr

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.

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