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Sequential phases of cortical specification involve Neurogenin ‐dependent and ‐independent pathways
Author(s) -
Schuurmans Carol,
Armant Olivier,
Nieto Marta,
Stenman Jan M,
Britz Olivier,
Klenin Natalia,
Brown Craig,
Langevin LisaMarie,
Seibt Julie,
Tang Hua,
Cunningham James M,
Dyck Richard,
Walsh Christopher,
Campbell Kenny,
Polleux Franck,
Guillemot François
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600278
Subject(s) - biology , computational biology , neuroscience
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.