title: The transcriptional repressor Mecp2 regulates terminal neuronal differentiation.
abstract: Rett syndrome (RTT) is a severe neurodevelopmental disorder with features of autism that results from mutation of the gene encoding the transcriptional repressor methyl-CpG binding protein (MECP2). The consequences of loss of a transcription factor may be complex, affecting the expression of many proteins, thus limiting understanding of this class of diseases and impeding therapeutic strategies. This is true for RTT. Neither the cell biological mechanism(s) nor the developmental stage affected by MECP2 deficiency is known. In vivo analysis of the olfactory system demonstrates that Mecp2 deficiency leads to a transient delay in the terminal differentiation of olfactory neurons. This delay in maturation disrupts axonal targeting in the olfactory bulb, resulting in abnormal axonal projections, subglomerular disorganization, and a persistent reduction in glomerular size. These results indicate a critical cell biological function for Mecp2 in mediating the final stages of neuronal development.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Valéry
authors.initials: V
authors.lastname: Matarazzo
authors.forename: Deborah
authors.initials: D
authors.lastname: Cohen
authors.forename: Amy M
authors.initials: AM
authors.lastname: Palmer
authors.forename: P Jeanette
authors.initials: PJ
authors.lastname: Simpson
authors.forename: Babar
authors.initials: B
authors.lastname: Khokhar
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Pan
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Ronnett
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D019581:Neuropil / Q000166:cytology / Q000378:metabolism; D009830:Olfactory Bulb / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D051842:Olfactory Marker Protein; D009833:Olfactory Pathways / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D019922:GAP-43 Protein; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D012097:Repressor Proteins