PubAg

Main content area

Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus

Author:
Breunig, Joshua J., Silbereis, John, Vaccarino, Flora M., Šestan, Nenad, Rakic, Pasko
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.51 pp. 20558-20563
ISSN:
0027-8424
Subject:
adults, cell cycle, gene overexpression, hippocampus, mice, neonates, neurogenesis, neurons, stem cells
Abstract:
The lifelong addition of neurons to the hippocampus is a remarkable form of structural plasticity, yet the molecular controls over proliferation, neuronal fate determination, survival, and maturation are poorly understood. Expression of Notch1 was found to change dynamically depending on the differentiation state of neural precursor cells. Through the use of inducible gain- and loss-of-function of Notch1 mice we show that this membrane receptor is essential to these distinct processes. We found in vivo that activated Notch1 overexpression induces proliferation, whereas γ-secretase inhibition or genetic ablation of Notch1 promotes cell cycle exit, indicating that the level of activated Notch1 regulates the magnitude of neurogenesis from postnatal progenitor cells. Abrogation of Notch signaling in vivo or in vitro leads to a transition from neural stem or precursor cells to transit-amplifying cells or neurons. Further, genetic Notch1 manipulation modulates survival and dendritic morphology of newborn granule cells. These results provide evidence for the expansive prevalence of Notch signaling in hippocampal morphogenesis and plasticity, suggesting that Notch1 could be a target of diverse traumatic and environmental modulators of adult neurogenesis.
Agid:
2354753