Abstract
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 language | English |
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Journal | Neurobiology of Disease |
Volume | 33 |
Issue number | 2 |
Pages (from-to) | 250-259 |
Number of pages | 10 |
ISSN | 0969-9961 |
DOIs | |
Publication status | Published - 2009 |
MoE publication type | A1 Journal article-refereed |
Fields of Science
- 311 Basic medicine
- 118 Biological sciences
- 515 Psychology