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PMID: 19620975 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry.

Nature neuroscience ·Vol. 12 ·No. 8 ·2009-08-00 ·Pages 1020-7

Bond AM, Vangompel MJ, Sametsky EA, Clark MF, Savage JC, Disterhoft JF, Kohtz JD

Abstract

Genomic studies demonstrate that, although the majority of the mammalian genome is transcribed, only about 2% of these transcripts are code for proteins. We investigated how the long, polyadenylated Evf2 noncoding RNA regulates transcription of the homeodomain transcription factors DLX5 and DLX6 in the developing mouse forebrain. We found that, in developing ventral forebrain, Evf2 recruited DLX and MECP2 transcription factors to important DNA regulatory elements in the Dlx5/6 intergenic region and controlled Dlx5, Dlx6 and Gad1 expression through trans and cis-acting mechanisms. Evf2 mouse mutants had reduced numbers of GABAergic interneurons in early postnatal hippocampus and dentate gyrus. Although the numbers of GABAergic interneurons and Gad1 RNA levels returned to normal in Evf2 mutant adult hippocampus, reduced synaptic inhibition occurred. These results suggest that noncoding RNA-dependent balanced gene regulation in embryonic brain is critical for proper formation of GABA-dependent neuronal circuitry in adult brain.

MeSH Terms
Animals Gene Expression Regulation, Developmental/genetics Glutamate Decarboxylase/genetics,metabolism Hippocampus/cytology,embryology,metabolism Homeodomain Proteins/genetics,metabolism Interneurons/metabolism Methyl-CpG-Binding Protein 2/genetics,metabolism Mice Mice, Knockout Mutation/genetics Neural Pathways/cytology,embryology,metabolism Organ Culture Techniques RNA, Messenger/metabolism RNA, Untranslated/genetics gamma-Aminobutyric Acid/metabolism
Chemicals
Dlx5 protein, mouse Dlx6 protein, mouse Homeodomain Proteins Mecp2 protein, mouse Methyl-CpG-Binding Protein 2 RNA, Messenger RNA, Untranslated gamma-Aminobutyric Acid Glutamate Decarboxylase glutamate decarboxylase 1
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bond Allison M
Developmental Biology and Department of Pediatrics, Children's Memorial Hospital and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Vangompel Michael J W
Sametsky Evgeny A
Clark Mary F
Savage Julie C
Disterhoft John F
Kohtz Jhumku D
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2371
Published
2009-08-00
Epub
2009-00-20
Pages
1020-7
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC3203213
Subset
IM
Grants
NICHD NIH HHS · R01 HD044745 · United States
NIMH NIH HHS · R01 MH047340 · United States
NICHD NIH HHS · R21 HD049875 · United States
NIA NIH HHS · R37 AG008796 · United States
NICHD NIH HHS · R21 HD049875-02 · United States
NIA NIH HHS · R01 AG017139 · United States
NICHD NIH HHS · R01 HD044745-05 · United States
External Links
PubMed source DOI: 10.1038/nn.2371 PMC Full Text View journal details
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