Sequential phases of cortical specificationinvolve Neurogenin-dependentand -independent pathways
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.
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