TY - JOUR T1 - Essential Roles of Notch Signaling in Maintenance of Neural Stem Cells in Developing and Adult Brains JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3489 LP - 3498 DO - 10.1523/JNEUROSCI.4987-09.2010 VL - 30 IS - 9 AU - Itaru Imayoshi AU - Masayuki Sakamoto AU - Masahiro Yamaguchi AU - Kensaku Mori AU - Ryoichiro Kageyama Y1 - 2010/03/03 UR - http://www.jneurosci.org/content/30/9/3489.abstract N2 - Activation of Notch signaling induces the expression of transcriptional repressor genes such as Hes1, leading to repression of proneural gene expression and maintenance of neural stem/progenitor cells. However, a requirement for Notch signaling in the telencephalon was not clear, because in Hes1;Hes3;Hes5 triple-mutant mice, neural stem/progenitor cells are depleted in most regions of the developing CNS, but not in the telencephalon. Here, we investigated a role for Notch signaling in the telencephalon by generating tamoxifen-inducible conditional knock-out mice that lack Rbpj, an intracellular signal mediator of all Notch receptors. When Rbpj was deleted in the embryonic brain, almost all telencephalic neural stem/progenitor cells prematurely differentiated into neurons and were depleted. When Rbpj was deleted in the adult brain, all neural stem cells differentiated into transit-amplifying cells and neurons. As a result, neurogenesis increased transiently, but 3 months later all neural stem cells were depleted and neurogenesis was totally lost. These results indicated an absolute requirement of Notch signaling for the maintenance of neural stem cells and a proper control of neurogenesis in both embryonic and adult brains. ER -