@article{76b30aaac1a540f0bd8c3c2b194e3607,
title = "Visualization of spatiotemporal activation of Notch signaling: Live monitoring and significance in neural development",
abstract = "Notch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address this issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these findings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development.",
keywords = "Astrocyte, EGFP, Gliogenesis, Hes1, Neural progenitors, Neural stem cell, Notch, RBP-J, Self-renewal, Venus",
author = "Jun Kohyama and Akinori Tokunaga and Yuko Fujita and Hiroyuki Miyoshi and Takeharu Nagai and Atsushi Miyawaki and Keiko Nakao and Yumi Matsuzaki and Hideyuki Okano",
note = "Funding Information: We are grateful to Drs. Takuya Shimazaki, Kazunobu Sawamoto, Yukiko Gotoh, and Ola Hermanson for their critical reading of the manuscript and to Hiroko Kouike for her assistance with the FACS analysis. We also thank Drs. Tasuku Honjo for providing the TP-1 luciferase plasmid, Raphael Kopan and Ryoichiro Kageyama for the Hes1p-luciferase plasmids, Masato Nakafuku for the Notch1 expression vectors, and Roger Tsien for the mRFP construct. This work was supported by grants to H.O. from the Japanese Ministry of Education, Culture, Sports, Science and Technology and the Japan Science and Technology Corporation (CREST) and by a grant-in-aid to Keio University from the 21st Century COE Program of the Ministry of Education, Culture, Sports, Science and Technology, Japan. ",
year = "2005",
month = oct,
day = "1",
doi = "10.1016/j.ydbio.2005.08.003",
language = "English",
volume = "286",
pages = "311--325",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",
}