Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain

John C. Silbereis, Hiroko Nobuta, Hui Hsin Tsai, Vivi M. Heine, Gabriel L. McKinsey, Dimphna H. Meijer, MacKenzie A. Howard, Magdalena Petryniak, Gregory Potter, John A. Alberta, Scott C. Baraban, Charles D. Stiles, John L R Rubenstein, David H. Rowitch

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Abnormal GABAergic interneuron density, and imbalance of excitatory versus inhibitory tone, is thought to result in epilepsy, neurodevelopmental disorders, and psychiatric disease. Recent studies indicate that interneuron cortical density is determined primarily by the size of the precursor pool inthe embryonic telencephalon. However, factors essential for regulating interneuron allocation from telencephalic multipotent precursors are poorly understood. Here we report that Olig1 represses production of GABAergic interneurons throughout the mouse brain. Olig1 deletion in mutant mice results in ectopic expression and upregulation of Dlx1/2 genes in the ventral medial ganglionic eminences and adjacent regions of the septum, resulting in an ~30% increase in adult cortical interneuron numbers. We show that Olig1 directly represses the. Dlx1/2 I12b intergenic enhancer and that Dlx1/2 functions genetically downstream of Olig1. These findings establish Olig1 as an essential repressor of. Dlx1/2 and interneuron production in developing mammalian brain.

Original languageEnglish (US)
Pages (from-to)574-587
Number of pages14
JournalNeuron
Volume81
Issue number3
DOIs
StatePublished - Feb 5 2014

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Interneurons
Brain
Telencephalon
Median Eminence
Psychiatry
Epilepsy
Up-Regulation
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Silbereis, J. C., Nobuta, H., Tsai, H. H., Heine, V. M., McKinsey, G. L., Meijer, D. H., ... Rowitch, D. H. (2014). Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain. Neuron, 81(3), 574-587. https://doi.org/10.1016/j.neuron.2013.11.024

Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain. / Silbereis, John C.; Nobuta, Hiroko; Tsai, Hui Hsin; Heine, Vivi M.; McKinsey, Gabriel L.; Meijer, Dimphna H.; Howard, MacKenzie A.; Petryniak, Magdalena; Potter, Gregory; Alberta, John A.; Baraban, Scott C.; Stiles, Charles D.; Rubenstein, John L R; Rowitch, David H.

In: Neuron, Vol. 81, No. 3, 05.02.2014, p. 574-587.

Research output: Contribution to journalArticle

Silbereis, JC, Nobuta, H, Tsai, HH, Heine, VM, McKinsey, GL, Meijer, DH, Howard, MA, Petryniak, M, Potter, G, Alberta, JA, Baraban, SC, Stiles, CD, Rubenstein, JLR & Rowitch, DH 2014, 'Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain', Neuron, vol. 81, no. 3, pp. 574-587. https://doi.org/10.1016/j.neuron.2013.11.024
Silbereis JC, Nobuta H, Tsai HH, Heine VM, McKinsey GL, Meijer DH et al. Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain. Neuron. 2014 Feb 5;81(3):574-587. https://doi.org/10.1016/j.neuron.2013.11.024
Silbereis, John C. ; Nobuta, Hiroko ; Tsai, Hui Hsin ; Heine, Vivi M. ; McKinsey, Gabriel L. ; Meijer, Dimphna H. ; Howard, MacKenzie A. ; Petryniak, Magdalena ; Potter, Gregory ; Alberta, John A. ; Baraban, Scott C. ; Stiles, Charles D. ; Rubenstein, John L R ; Rowitch, David H. / Olig1 Function Is Required to Repress Dlx1/2 and Interneuron Production in Mammalian Brain. In: Neuron. 2014 ; Vol. 81, No. 3. pp. 574-587.
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