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  • The EMBO Journal (2004) 23, 2892 - 2902
  • doi:10.1038/sj.emboj.7600278

Published online: 1 July 2004

Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways

Carol Schuurmans1,2, Olivier Armant1,3, Marta Nieto4, Jan M Stenman5, Olivier Britz1,3, Natalia Klenin2, Craig Brown6, Lisa-Marie Langevin2, Julie Seibt7, Hua Tang8, James M Cunningham8, Richard Dyck6, Christopher Walsh4, Kenny Campbell5, Franck Polleux7,9 and François Guillemot1,3

  1. IGBMC, Illkirch, CU de Strasbourg, France
  2. Genes and Development Research Group, University of Calgary, Calgary, AB, Canada
  3. Division of Molecular Neurobiology, NIMR, The Ridgeway, Mill Hill, London, UK
  4. Beth Israel Deaconess Medical Center, HHMI, Harvard Medical School, Boston, MA, USA
  5. Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH, USA
  6. Department of Psychology, University of Calgary, Calgary, AB, Canada
  7. INSERM U371, Bron, France
  8. Department of Medicine, Harvard Medical School, Boston, MA, USA
  9. Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA

Correspondence to:

Carol Schuurmans, Genes and Development Research Group, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, Canada T2N 4N1. Tel.: +1 403 220 3025; Fax: +1 403 270 2211; E-mail: cschuurm@ucalgary.ca

François Guillemot, Division of Molecular Neurobiology, NIMR, Mill Hill, London. Tel.: +44 20 8816 2740; Fax: +44 20 8816 2109; E-mail: fguille@nimr.mrc.ac.uk

Received 27 January 2004; Accepted 25 May 2004

Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons.

  • Keywords:

    • laminar specification,
    • neocortex,
    • Neurogenins,
    • neurotransmitter phenotype