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An intrinsic mechanism of corticogenesis from embryonic stem cells

Author

Listed:
  • Nicolas Gaspard

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Tristan Bouschet

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Raphael Hourez

    (Laboratory of Neurophysiology, Université Libre de Bruxelles (ULB), 808 Route de Lennik, B-1070 Brussels, Belgium)

  • Jordane Dimidschstein

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Gilles Naeije

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Jelle van den Ameele

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Ira Espuny-Camacho

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Adèle Herpoel

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Lara Passante

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

  • Serge N. Schiffmann

    (Laboratory of Neurophysiology, Université Libre de Bruxelles (ULB), 808 Route de Lennik, B-1070 Brussels, Belgium)

  • Afsaneh Gaillard

    (Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, Centre National de la Recherche Scientifique (CNRS), 40 avenue du recteur Pineau, Poitiers, F-86022, France)

  • Pierre Vanderhaeghen

    (IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles (ULB))

Abstract

The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.

Suggested Citation

  • Nicolas Gaspard & Tristan Bouschet & Raphael Hourez & Jordane Dimidschstein & Gilles Naeije & Jelle van den Ameele & Ira Espuny-Camacho & Adèle Herpoel & Lara Passante & Serge N. Schiffmann & Afsaneh , 2008. "An intrinsic mechanism of corticogenesis from embryonic stem cells," Nature, Nature, vol. 455(7211), pages 351-357, September.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7211:d:10.1038_nature07287
    DOI: 10.1038/nature07287
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    Cited by:

    1. Jingyu Zhang & Hengyu Chen & Ruoyan Li & David A Taft & Guang Yao & Fan Bai & Jianhua Xing, 2019. "Spatial clustering and common regulatory elements correlate with coordinated gene expression," PLOS Computational Biology, Public Library of Science, vol. 15(3), pages 1-16, March.
    2. Yongcheng Jin & Ellina Mikhailova & Ming Lei & Sally A. Cowley & Tianyi Sun & Xingyun Yang & Yujia Zhang & Kaili Liu & Daniel Catarino da Silva & Luana Campos Soares & Sara Bandiera & Francis G. Szele, 2023. "Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Delfina M. Romero & Karine Poirier & Richard Belvindrah & Imane Moutkine & Anne Houllier & Anne-Gaëlle LeMoing & Florence Petit & Anne Boland & Stephan C. Collins & Mariano Soiza-Reilly & Binnaz Yalci, 2022. "Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Balazs V. Varga & Maryam Faiz & Helena Pivonkova & Gabriel Khelifi & Huijuan Yang & Shangbang Gao & Emma Linderoth & Mei Zhen & Ragnhildur Thora Karadottir & Samer M. Hussein & Andras Nagy, 2022. "Signal requirement for cortical potential of transplantable human neuroepithelial stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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