MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions

Kishi, Noriyuki; Macklis, Jeffrey D.

doi:10.1016/j.mcn.2004.07.006

Cited by 445Genetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions

Kishi, Noriyuki, Macklis, Jeffrey D.·2004·Molecular and Cellular Neuroscience

DOI 10.1016/j.mcn.2004.07.006

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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.

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Loss of MeCp2 results in reduced brain weight and thinning of the neocortex in some mouse models.
“Loss of MeCp2 results in reduced brain weight [67, 126], with thinning of the neocortex described in some mouse models [115, 200, 302].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [200]

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Authors: Kishi, N., & Macklis, J. D.
Affiliations: Harvard University (US)
Corresponding author: Macklis, Jeffrey D.
ORCID: Macklis, Jeffrey D.
Venue: Molecular and Cellular Neuroscience
Publisher: Elsevier BV
Published: 2004-11
Volume: 27
Issue: 3
Pages: 306-321
ISSN: 1044-7431 (ISSN-L)
DOI: 10.1016/j.mcn.2004.07.006
OpenAlex: W2000313340
Cited by: 445
References: 78
Citations by year: 2026: 7 · 2025: 19 · 2024: 9 · 2023: 11 · 2022: 16 · 2021: 19 · 2020: 16 · 2019: 12 · 2018: 21 · 2017: 21 · 2016: 25 · 2015: 27 · 2014: 18 · 2013: 30 · 2012: 32
FWCI: 8.92
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular and Cellular Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS045523, NS 41590, NS45523)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD18655, P30HD018655)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: MeCP2, Rett syndrome, neuronal maturation, neural development, neocortex, neural precursor differentiation, dendritic branching, pyramidal neurons, cell fate determination, transcriptional repressor, Mecp2-null mice
MeSH terms: Animals, Cell Movement, Cells, Cultured, Chromosomal Proteins, Non-Histone, Dendrites, DNA-Binding Proteins, Female, Male, Mice, Inbred C57BL, Neurons, Repressor Proteins, Mice, Knockout, Mice, Methyl-CpG-Binding Protein 2

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MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions

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