Survey of MeCP2 in the Rett syndrome and the non-Rett syndrome brain

J Child Neurol. 2003 Oct;18(10):683-7. doi: 10.1177/08830738030180100601.


The clinical and neuropathologic aspects of Rett syndrome suggest that an arrest of brain development produces the phenotype, but it is not understood how the gene implicated in Rett syndrome, methyl-CpG protein 2 (MeCP2), is regulated during brain development. In this study, the ontogeny of MeCP2 is examined in the developing human brain and in the female Rett syndrome brain to evaluate the relationship between MeCP2 expression and brain development in health and disease, respectively. Immunocytochemistry using an antibody to the C-terminal region of the protein was performed in paraffin sections of the developing brain to define the age and the sites of MeCP2 protein expression. In development, there is no MeCP2 expression in the germinal matrix or in the progenitor cells. At 10 to 14 weeks' gestation, the neurons of the brain stem and the Cajal-Retzius and subplate neurons of the cortex express MeCP2. By midgestation, some neurons of the basal ganglia express MeCP2, and at late gestation, the most mature cortical neurons in the lower cortical layers are positive. The postnatal cortex continues to increase its expression of neuronal MeCP2. In the Rett syndrome brain, fewer neurons express MeCP2 than in the normal brain. This reduction is most apparent in the brain stem and thalamus. The neurons of the cerebral cortex show the least reduction. We conclude that the regulation of MeCP2 abundance is related to human brain development, being expressed in neurons when they appear mature. In Rett syndrome, however, the expression pattern of MeCP2 does not completely resemble that of the normal immature brain, suggesting that the maintenance of MeCP2 might be determined in specific neurons by factors other than those controlling maturation. In the developing brain, synaptic activity and plasticity could be necessary to maintain MeCP2 in selected neuronal populations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Autopsy
  • Brain / embryology
  • Brain / growth & development*
  • Brain / metabolism*
  • Brain Stem / growth & development
  • Brain Stem / metabolism
  • Case-Control Studies
  • Cerebellum / growth & development
  • Cerebellum / metabolism
  • Child
  • Chromosomal Proteins, Non-Histone*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fetus
  • Frontal Lobe / growth & development
  • Frontal Lobe / metabolism
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • Infant
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins*
  • Rett Syndrome / metabolism*
  • Stem Cells / metabolism
  • Substantia Nigra / growth & development
  • Substantia Nigra / metabolism
  • Thalamus / growth & development
  • Thalamus / metabolism


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins