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| Status |
Public on Jul 27, 2010 |
| Title |
Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Beyer RP, Bedognia F, Hodgea RD, Elsena GE, Nelson BR, Dazaa RA, Rubensteind JL, Hevner RF |
| Citation(s) |
20615956, 34321999 |
| Submission date |
Jun 15, 2010 |
| Last update date |
Aug 03, 2021 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (2) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA127649 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22371_RAW.tar |
123.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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