title: Olig1 function is required to repress dlx1/2 and interneuron production in Mammalian brain.
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 in the 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.
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors: John C
authors: JC
authors: Silbereis
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors: Hiroko
authors: H
authors: Nobuta
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors: Hui-Hsin
authors: HH
authors: Tsai
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Vivi M
authors: VM
authors: Heine
authors: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Gabriel L
authors: GL
authors: McKinsey
authors: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Dimphna H
authors: DH
authors: Meijer
authors: Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Mackenzie A
authors: MA
authors: Howard
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Magda A
authors: MA
authors: Petryniak
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Gregory B
authors: GB
authors: Potter
authors: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: John A
authors: JA
authors: Alberta
authors: Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Scott C
authors: SC
authors: Baraban
authors: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Charles D
authors: CD
authors: Stiles
authors: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: John L R
authors: JL
authors: Rubenstein
authors: Department of Pediatrics, Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: rowitchd@peds.ucsf.edu.
authors: David H
authors: DH
authors: Rowitch
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005968:Glutamate Decarboxylase; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D014157:Transcription Factors; C088334:Distal-less homeobox proteins; C494786:Olig1 protein, mouse; C490035:Sp8 protein, mouse; C485177:Vax1 protein, mouse; C402565:glutamate decarboxylase 1