Aberrant differentiation of glutamatergic cells in neocortex of mouse model for fragile X syndrome.
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.
Tervonen
Topi A
TA
Neuroscience Center, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
Louhivuori
Verna
V
Sun
Xiaohong
X
Hokkanen
Marie-Estelle
ME
Kratochwil
Claudius F
CF
Zebryk
Pawel
P
Castrén
Eero
E
Castrén
Maija L
ML
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000502:physiology; D005600:Fragile X Syndrome / Q000196:embryology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D019579:Neocortex / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017966:Pyramidal Cells / Q000254:growth & development; D013234:Stem Cells / Q000166:cytology*; D020825:T-Box Domain Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D027341:Excitatory Amino Acid Transporter 1; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D020825:T-Box Domain Proteins; C491198:Eomes protein, mouse; C497683:FMR1 protein, human; C086936:Fabp7 protein, mouse; C497684:Fmr1 protein, mouse; C493393:Slc1a3 protein, mouse; C492271:Tbr1 protein, mouse