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

Neurobiology of Disease

Marie-Estelle Hokkanen¹  Maija L. Castrén²  Verna Louhivuori³  Eero Castrén⁴  Xiaohong Sun⁴  Pawel Zebryk⁴  Topi A. Tervonen⁴  Claudius F. Kratochwil⁴ 

[1] Department of Neurology, the Fourth Affiliated Hospital of China Medical University, Liaoning 110032, China;Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland;Department of Biomedicine/Physiology, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland;Neuroscience Center, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland;

关键词: Fmr1 knockout;    Brain development;    Differentiation;    Glutamatergic;    Neural progenitor cell;    Tbr2;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 I304N 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.

【 授权许可】

Unknown