title: MeCP2 regulates activity-dependent transcriptional responses in olfactory sensory neurons.
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.
authors.affiliation: Department of Cell Biology and Human Anatomy.
authors.forename: Wooje
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Kwangju Women's University, Gwang ju 506-713, South Korea and.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Yun
authors.affiliation: Department of Medical Microbiology and Immunology.
authors.forename: Rima
authors.initials: R
authors.lastname: Woods
authors.affiliation: Department of Medical Microbiology and Immunology.
authors.forename: Keith
authors.initials: K
authors.lastname: Dunaway
authors.affiliation: Department of Medical Microbiology and Immunology.
authors.forename: Dag H
authors.initials: DH
authors.lastname: Yasui
authors.affiliation: Department of Medical Microbiology and Immunology, UC Davis Genome Center, University of California at Davis, School of Medicine, Davis, CA 95616, USA, UC Davis MIND Institute, Sacramento, CA 95817, USA.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Lasalle
authors.affiliation: Department of Cell Biology and Human Anatomy, qzgong@ucdavis.edu.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Gong
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D015820:Cadherins / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D000091363:Protocadherins; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D014158:Transcription, Genetic
chemical_list: D015820:Cadherins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; C527873:PCDH20 protein, mouse; D000091363:Protocadherins