Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development.
In the developing CNS, subtypes of neurons and glial cells are generated according to a schedule that is defined by cell-intrinsic mechanisms that function at the progenitor-cell level. However, no critical molecular switch for the temporal specification of CNS progenitor cells has been identified. We found that chicken ovalbumin upstream promoter-transcription factor I and II (Coup-tfI and Coup-tfII, also known as Nr2f1 and Nr2f2) are required for the temporal specification of neural stem/progenitor cells (NSPCs), including their acquisition of gliogenic competence, as demonstrated by their responsiveness to gliogenic cytokines. COUP-TFI and II are transiently co-expressed in the ventricular zone of the early embryonic CNS. The double knockdown of Coup-tfI/II in embryonic stem cell (ESC)-derived NSPCs and the developing mouse forebrain caused sustained neurogenesis and the prolonged generation of early-born neurons. These findings reveal a part of the timer mechanisms for generating diverse types of neurons and glial cells during CNS development.
Naka
Hayato
H
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Nakamura
Shiho
S
Shimazaki
Takuya
T
Okano
Hideyuki
H
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D051838:COUP Transcription Factor I / Q000235:genetics / Q000378:metabolism*; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D034741:RNA, Small Interfering / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism
D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D034741:RNA, Small Interfering; D014404:Tubulin; C462941:beta3 tubulin, mouse; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine