Defects during Mecp2 Null Embryonic Cortex Development Precede the Onset of Overt Neurological Symptoms

Francesco Bedogni, Clementina Cobolli Gigli, Davide Pozzi, Riccardo L. Rossi, Linda Scaramuzza, G. Rossetti, Massimiliano Pagani, Charlotte Kilstrup-Nielsen, Michela Matteoli, Nicoletta Landsberger

Research output: Contribution to journalArticle

Abstract

MeCP2 is associated with several neurological disorders; of which, Rett syndrome undoubtedly represents the most frequent. Its molecular roles, however, are still unclear, and data from animal models often describe adult, symptomatic stages, while MeCP2 functions during embryonic development remain elusive. We describe the pattern and timing of Mecp2 expression in the embryonic neocortex highlighting its low but consistent expression in virtually all cells and show the unexpected occurrence of transcriptional defects in the Mecp2 null samples at a stage largely preceding the onset of overt symptoms. Through the deregulated expression of ionic channels and glutamatergic receptors, the lack of Mecp2 during early neuronal maturation leads to the reduction in the neuronal responsiveness to stimuli. We suggest that such features concur to morphological alterations that begin affecting Mecp2 null neurons around the perinatal age and become evident later in adulthood. We indicate MeCP2 as a key modulator of the transcriptional mechanisms regulating cerebral cortex development. Neurological phenotypes of MECP2 patients could thus be the cumulative result of different adverse events that are already present at stages when no obvious signs of the pathology are evident and are worsened by later impairments affecting the central nervous system during maturation and maintenance of its functionality.

Original languageEnglish
Pages (from-to)2517-2529
Number of pages13
JournalCerebral Cortex
Volume26
Issue number6
DOIs
Publication statusPublished - 2016

Keywords

  • Embryonic cerebral cortex development
  • Intrinsic neuronal excitability
  • MeCP2 null cortex
  • Neurological disorders
  • Transcriptome

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience

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  • Cite this

    Bedogni, F., Gigli, C. C., Pozzi, D., Rossi, R. L., Scaramuzza, L., Rossetti, G., Pagani, M., Kilstrup-Nielsen, C., Matteoli, M., & Landsberger, N. (2016). Defects during Mecp2 Null Embryonic Cortex Development Precede the Onset of Overt Neurological Symptoms. Cerebral Cortex, 26(6), 2517-2529. https://doi.org/10.1093/cercor/bhv078