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PMID: 15229646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 23 ·No. 14 ·2004-07-21 ·Pages 2892-902

Schuurmans C, Armant O, Nieto M, Stenman JM, Britz O, Klenin N, Brown C, Langevin LM, Seibt J, Tang H, Cunningham JM, Dyck R, Walsh C, Campbell K, Polleux F, Guillemot F

Abstract

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.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors Eye Proteins/genetics,metabolism Gene Expression Profiling Gene Expression Regulation, Developmental Homeodomain Proteins/genetics,metabolism Mice Mice, Knockout Mice, Mutant Strains Mice, Transgenic Mutation Neocortex/embryology,metabolism Nerve Tissue Proteins/genetics,metabolism Neurons/cytology PAX6 Transcription Factor Paired Box Transcription Factors Protein Array Analysis Receptors, Cytoplasmic and Nuclear/metabolism Repressor Proteins/genetics,metabolism Transcription Factors/genetics,metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors Eye Proteins Homeodomain Proteins Nerve Tissue Proteins Neurog2 protein, mouse Nr2e1 protein, mouse PAX6 Transcription Factor Paired Box Transcription Factors Pax6 protein, mouse Receptors, Cytoplasmic and Nuclear Repressor Proteins Transcription Factors Neurog1 protein, mouse
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Schuurmans Carol
IGBMC, Illkirch, CU de Strasbourg, France.
Armant Olivier
Nieto Marta
Stenman Jan M
Britz Olivier
Klenin Natalia
Brown Craig
Langevin Lisa-Marie
Seibt Julie
Tang Hua
Cunningham James M
Dyck Richard
Walsh Christopher
Campbell Kenny
Polleux Franck
Guillemot François
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600278
Published
2004-07-21
Epub
2004-00-01
Pages
2892-902
Language
English
Region
England
NLM ID
8208664
PMCID
PMC514942
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600278 PMC Full Text View journal details
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