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

作者：Tervonen Topi A; Louhivuori Verna; Sun Xiaohong; Hokkanen Marie Estelle; Kratochwil Claudius F; Zebryk Pawel; Castren Eero; Castren Maija L^*

来源：Neurobiology of Disease, 2009, 33(2): 250-259.

DOI：10.1016/j.nbd.2008.10.010

• Fmr1 knockout
• Brain development
• Differentiation
• Glutamatergic
• Neural progenitor cell
• Tbr2
• Tbr1
• BrdU
• In utero electroporation

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.

• 出版日期2009-2
• 单位中国医科大学