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

Francesco Bedogni, Rebecca D. Hodge, Gina E. Elsen, Branden R. Nelson, Ray A M Daza, Richard P. Beyer, Theo K. Bammler, John L R Rubenstein, Robert F. Hevner

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)13129-13134
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number29
DOIs
Publication statusPublished - Jul 20 2010

Keywords

  • Arealization
  • Auts2
  • Microarray

ASJC Scopus subject areas

  • General

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    Bedogni, F., Hodge, R. D., Elsen, G. E., Nelson, B. R., Daza, R. A. M., Beyer, R. P., Bammler, T. K., Rubenstein, J. L. R., & Hevner, R. F. (2010). Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex. Proceedings of the National Academy of Sciences of the United States of America, 107(29), 13129-13134. https://doi.org/10.1073/pnas.1002285107