title: Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains.
abstract: 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.
authors.affiliation: Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Imayoshi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Kensaku
authors.initials: K
authors.lastname: Mori
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000254:growth & development
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009498:Neurotoxins; C497571:Rbpj protein, mouse; D051880:Receptors, Notch