Transcriptomics

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Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex


ABSTRACT: Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons. Mouse E14.5 neocortices and Postnatal day (P) 0.5 brains: E14.5 neocortices KO, 3; E14.5 neocortices WT, 3; Postnatal day (P) 0.5 brains frontal WT, 4; Postnatal day (P) 0.5 brains frontal KO, 4; Postnatal day (P) 0.5 brains parietal WT, 4; Postnatal day (P) 0.5 brains parietal KO, 4; Postnatal day (P) 0.5 brains occipital WT, 4; Postnatal day (P) 0.5 brains occipital KO, 4.

ORGANISM(S): Mus musculus  

SUBMITTER: Robert F Hevner   John L Rubensteind  Richard Beyer  Ray A Dazaa  Richard P Beyer  Gina E Elsena  Francesco Bedognia  Branden R Nelson  Rebecca D Hodgea 

PROVIDER: E-GEOD-22371 | ArrayExpress | 2010-07-27

SECONDARY ACCESSION(S): GSE22371PRJNA127649

REPOSITORIES: GEO, ArrayExpress

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Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex.

Bedogni Francesco F   Bedogni Francesco F   Hodge Rebecca D RD   Elsen Gina E GE   Nelson Branden R BR   Daza Ray A M RA   Beyer Richard P RP   Bammler Theo K TK   Rubenstein John L R JL   Hevner Robert F RF  

Proceedings of the National Academy of Sciences of the United States of America 20100706 29


Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6  ...[more]

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