title: Oscillatory control of factors determining multipotency and fate in mouse neural progenitors.
abstract: The basic helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate fate choice of neurons, astrocytes, and oligodendrocytes, respectively. These same factors are coexpressed by neural progenitor cells. Here, we found by time-lapse imaging that these factors are expressed in an oscillatory manner by mouse neural progenitor cells. In each differentiation lineage, one of the factors becomes dominant. We used optogenetics to control expression of Ascl1 and found that, although sustained Ascl1 expression promotes neuronal fate determination, oscillatory Ascl1 expression maintains proliferating neural progenitor cells. Thus, the multipotent state correlates with oscillatory expression of several fate-determination factors, whereas the differentiated state correlates with sustained expression of a single factor.
authors.affiliation: Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Imayoshi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Isomura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Harima
authors.forename: Kyogo
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kori
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyachi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Ishidate
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D055879:Gene Knock-In Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D062308:Optogenetics; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism; D000072056:Transcription Factor HES-1; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D000072056:Transcription Factor HES-1; C499317:Ascl1 protein, mouse; C489734:Hes1 protein, mouse; C512773:Olig2 protein, mouse