Aberrant differentiation of glutamatergic cells in neocortex of mouse model for fragile X syndrome

Topi A Tervonen, Verna Louhivuori, Xiaohong Sun, Marie-Estelle Hokkanen, Claudius F Kratochwil, Pawel Zebryk, Eero Castren, Maija Castren

Research output: Contribution to journalArticleScientificpeer-review


The lack of fragile X mental retardation protein (FMRP) causes fragile X syndrome, a common form of inherited mental retardation. Our previous studies revealed alterations in the differentiation of FMRP-deficient neural progenitors. Here, we show abnormalities in neurogenesis in the mouse and human embryonic FMRP-deficient brain as well as after in utero transfection of 1304N mutated FMRP, which acts in a dominant negative manner in the wild-type mouse brain. Progenitors accumulated abnormally in the subventricular zone of the embryonic Fmr1-knockout (Fmr1-KO) mouse neocortex. An increased density of cells expressing sequentially an intermediate progenitor marker, T-box transcription factor (Tbr2), and a postmitotic neuron marker, T-brain 1 (Tbr1), indicated that the differentiation to glutamatergic cell lineages was particularly disturbed. These abnormalities were associated with an increased density of pyramidal cells of the layer V in the early postnatal neocortex suggesting a role for FMRP in the regulation of the differentiation of neocortical glutamatergic neurons. (C) 2008 Elsevier Inc. All rights reserved.
Original languageEnglish
JournalNeurobiology of Disease
Issue number2
Pages (from-to)250-259
Number of pages10
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 311 Basic medicine
  • 118 Biological sciences
  • 515 Psychology

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