RT Journal Article
SR Electronic
T1 Bre1a, a Histone H2B Ubiquitin Ligase, Regulates the Cell Cycle and Differentiation of Neural Precursor Cells
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3067
OP 3078
DO 10.1523/JNEUROSCI.3832-13.2014
VO 34
IS 8
A1 Yugo Ishino
A1 Yoshitaka Hayashi
A1 Masae Naruse
A1 Koichi Tomita
A1 Makoto Sanbo
A1 Takahiro Fuchigami
A1 Ryoji Fujiki
A1 Kenzo Hirose
A1 Yayoi Toyooka
A1 Toshihiko Fujimori
A1 Kazuhiro Ikenaka
A1 Seiji Hitoshi
YR 2014
UL http://www.jneurosci.org/content/34/8/3067.abstract
AB Cell cycle regulation is crucial for the maintenance of stem cell populations in adult mammalian tissues. During development, the cell cycle length in neural stem cells increases, which could be associated with their capabilities for self-renewal. However, the molecular mechanisms that regulate differentiation and cell cycle progression in embryonic neural stem cells remain largely unknown. Here, we investigated the function of Bre1a, a histone H2B ubiquitylation factor, which is expressed in most but not all of neural precursor cells (NPCs) in the developing mouse brain. We found that the knockdown of Bre1a in NPCs lengthened their cell cycle through the upregulation of p57kip2 and the downregulation of Cdk2. In addition, the knockdown of Bre1a increased the expression of Hes5, an effector gene of Notch signaling, through the action of Fezf1 and Fezf2 genes and suppressed the differentiation of NPCs. Our data suggest that Bre1a could be a bifunctional gene that regulates both the differentiation status and cell cycle length of NPCs. We propose a novel model that the Bre1a-negative cells in the ventricular zone of early embryonic brains remain undifferentiated and are selected as self-renewing neural stem cells, which increase their cell cycle time during development.