MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions - PubMed (original) (raw)
Comparative Study
MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions
Noriyuki Kishi et al. Mol Cell Neurosci. 2004 Nov.
Abstract
Rett syndrome is a neurodevelopmental disorder and one of the causes of mental retardation and autistic behavior in girls, as well as in a small group of boys. It was recently discovered that mutation of the methyl-CpG-binding protein 2 (MECP2) gene encoding a transcriptional repressor on the X chromosome causes Rett syndrome. Although it is evident that phenotypes of MECP2 mutant mice that resemble those of Rett syndrome are attributable to lack of the MECP2 gene in the central nervous system (CNS), there is little understanding of the neuropathological abnormalities in the CNS of MECP2-null mice. Here, we investigated the developmental regulation and specific cellular expression of MECP2 during neural development both in vitro and in vivo. MECP2 is expressed in mature neurons, but not in astroglia or oligodendroglia, and is increasingly expressed during development of the mouse neocortex. In addition, in vitro culture studies suggest that MECP2 is expressed in more differentiated neurons rather than in less differentiated neuroblasts. Under in vitro conditions using neural precursor cultures, we find that MECP2 mutant neural precursors differentiate into morphologically mature neurons and glia, and no significant differences in differentiation are detected between cells from wild-type and MECP2 mutant mice, suggesting that MECP2 may play a different role in mice than it does in Xenopus embryos. In agreement with this hypothesis, neocortical projection layers in MECP2 -/y mice are thinner than those in wild-type mice, and pyramidal neurons in layer II/III in MECP2 -/y mice are smaller and less complex than those in wild-type mice. Taken together, our results indicate that MECP2 is involved in the maturation and maintenance of neurons, including dendritic arborization, rather than in cell fate decisions.
Similar articles
- Increased dendritic complexity and axonal length in cultured mouse cortical neurons overexpressing methyl-CpG-binding protein MeCP2.
Jugloff DG, Jung BP, Purushotham D, Logan R, Eubanks JH. Jugloff DG, et al. Neurobiol Dis. 2005 Jun-Jul;19(1-2):18-27. doi: 10.1016/j.nbd.2004.11.002. Neurobiol Dis. 2005. PMID: 15837557 - MeCP2 in neurons: closing in on the causes of Rett syndrome.
Caballero IM, Hendrich B. Caballero IM, et al. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R19-26. doi: 10.1093/hmg/ddi102. Hum Mol Genet. 2005. PMID: 15809268 Review. - Reduced proportion of Purkinje cells expressing paternally derived mutant Mecp2308 allele in female mouse cerebellum is not due to a skewed primary pattern of X-chromosome inactivation.
Watson CM, Pelka GJ, Radziewic T, Shahbazian MD, Christodoulou J, Williamson SL, Tam PP. Watson CM, et al. Hum Mol Genet. 2005 Jul 1;14(13):1851-61. doi: 10.1093/hmg/ddi191. Epub 2005 May 11. Hum Mol Genet. 2005. PMID: 15888476 - The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells.
Jung BP, Jugloff DG, Zhang G, Logan R, Brown S, Eubanks JH. Jung BP, et al. J Neurobiol. 2003 Apr;55(1):86-96. doi: 10.1002/neu.10201. J Neurobiol. 2003. PMID: 12605461 - Rett syndrome: of girls and mice--lessons for regression in autism.
Glaze DG. Glaze DG. Ment Retard Dev Disabil Res Rev. 2004;10(2):154-8. doi: 10.1002/mrdd.20030. Ment Retard Dev Disabil Res Rev. 2004. PMID: 15362175 Review.
Cited by
- Epigenetics in rare neurological diseases.
Roberts CT, Arezoumand KS, Kadar Shahib A, Davie JR, Rastegar M. Roberts CT, et al. Front Cell Dev Biol. 2024 Jul 23;12:1413248. doi: 10.3389/fcell.2024.1413248. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 39108836 Free PMC article. Review. - Developing AAV-delivered nonsense suppressor tRNAs for neurological disorders.
Wang J, Gao G, Wang D. Wang J, et al. Neurotherapeutics. 2024 Jul;21(4):e00391. doi: 10.1016/j.neurot.2024.e00391. Epub 2024 Jul 2. Neurotherapeutics. 2024. PMID: 38959711 Free PMC article. Review. - Nuclease-free precise genome editing corrects MECP2 mutations associated with Rett syndrome.
Bijlani S, Pang KM, Bugga LV, Rangasamy S, Narayanan V, Chatterjee S. Bijlani S, et al. Front Genome Ed. 2024 Mar 1;6:1346781. doi: 10.3389/fgeed.2024.1346781. eCollection 2024. Front Genome Ed. 2024. PMID: 38495533 Free PMC article. - Variable expression of MECP2, CDKL5, and FMR1 in the human brain: Implications for gene restorative therapies.
Zito A, Lee JT. Zito A, et al. Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2312757121. doi: 10.1073/pnas.2312757121. Epub 2024 Feb 22. Proc Natl Acad Sci U S A. 2024. PMID: 38386709 Free PMC article. - Non-CG DNA methylation and MeCP2 stabilize repeated tuning of long genes that distinguish closely related neuron types.
Moore JR, Nemera MT, D'Souza RD, Hamagami N, Clemens AW, Beard DC, Urman A, Mendoza VR, Gabel HW. Moore JR, et al. bioRxiv [Preprint]. 2024 Jan 30:2024.01.30.577861. doi: 10.1101/2024.01.30.577861. bioRxiv. 2024. PMID: 38352532 Free PMC article. Preprint.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases