Article

Impaired Adult Neurogenesis in Mice Lacking the Transcription Factor E2F1

Department of Neurology, University of Regensburg, D-93053, Regensburg, Germany; Division of Neuroscience, Children's Hospital, Boston, Massachusetts, 02115
Molecular and Cellular Neuroscience DOI:10.1006/mcne.2002.1176 pp.312-323

ABSTRACT 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.

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Keywords

adult brain
 
adult cerebellum
 
adult olfactory bulb
 
brains
 
cells—whether
 
dentate gyrus
 
E2F1 deficiency
 
growth factors
 
hippocampus
 
nervous system development
 
neural
 
Neuronal cell counts
 
neuronal cell numbers
 
newborn neurons
 
proliferation
 
proliferative zones
 
signaling cascades
 
significant cerebellar atrophy
 
various signals
 

Christiana M Cooper-Kuhn