MeCP2 regulates activity-dependent transcriptional responses in olfactory sensory neurons

Wooje Lee, Jung Mi Yun, Rima Woods, Keith Dunaway, Dag H. Yasui, Janine M. Lasalle, Qizhi Gong

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

During postnatal development, neuronal activity controls the remodeling of initially imprecise neuronal connections through the regulation of gene expression. MeCP2 binds to methylated DNA and modulates gene expression during neuronal development and MECP2 mutation causes the autistic disorder Rett syndrome. To investigate a role for MeCP2 in neuronal circuit refinement and to identify activity-dependent MeCP2 transcription regulations, we leveraged the precise organization and accessibility of olfactory sensory axons to manipulation of neuronal activity through odorant exposure in vivo. We demonstrate that olfactory sensory axons failed to develop complete convergence when Mecp2 is deficient in olfactory sensory neurons (OSNs) in an otherwise wild-type animal. Furthermore, we demonstrate that expression of selected adhesion genes was elevated in Mecp2-deficient glomeruli, while acute odor stimulation in control mice resulted in significantly reduced MeCP2 binding to these gene loci, correlating with increased expression. Thus, MeCP2 is required for both circuitry refinement and activity-dependent transcriptional responses in OSNs.

Original languageEnglish (US)
Pages (from-to)6366-6374
Number of pages9
JournalHuman Molecular Genetics
Volume23
Issue number23
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Medicine(all)

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