Impaired adult neurogenesis in mice lacking the transcription factor E2F1.
During nervous system development the fate of neural stem cells-whether to undergo proliferation, differentiation, or apoptosis-is controlled by various signals, such as growth factors. Here, we demonstrate that the transcription factor E2F1, which is targeted by several signaling cascades that are activated by growth factors, is involved in neurogenesis in the adult brain. When analyzing the brains of E2F1-deficient mice, we found significantly decreased stem cell and progenitor division in the proliferative zones of the lateral ventricle wall and the hippocampus. As a consequence, the production of newborn neurons in the adult olfactory bulb and dentate gyrus was decreased. Neuronal cell counts of the adult cerebellum revealed a mild but significant cerebellar atrophy, whereas neocortical neurons were unaffected, suggesting that E2F1 deficiency produces a predominantly postnatal phenotype. The results indicate an involvement of E2F1 in controlling proliferation and neuronal cell numbers in the postnatal and adult brain.
Cooper-Kuhn
Christiana M
CM
Department of Neurology, University of Regensburg, D-93053 Regensburg, Germany.
Vroemen
Maurice
M
Brown
Jason
J
Ye
Hong
H
Thompson
Margaret A
MA
Winkler
Jürgen
J
Kuhn
H Georg
HG
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D014157:Transcription Factors