title: A conserved nuclear receptor, Tailless, is required for efficient proliferation and prolonged maintenance of mushroom body progenitors in the Drosophila brain.
abstract: The intrinsic neurons of mushroom bodies (MBs), centers of olfactory learning in the Drosophila brain, are generated by a specific set of neuroblasts (Nbs) that are born in the embryonic stage and exhibit uninterrupted proliferation till the end of the pupal stage. Whereas MB provides a unique model to study proliferation of neural progenitors, the underlying mechanism that controls persistent activity of MB-Nbs is poorly understood. Here we show that Tailless (TLL), a conserved orphan nuclear receptor, is required for optimum proliferation activity and prolonged maintenance of MB-Nbs and ganglion mother cells (GMCs). Mutations of tll progressively impair cell cycle in MB-Nbs and cause premature loss of MB-Nbs in the early pupal stage. TLL is also expressed in MB-GMCs to prevent apoptosis and promote cell cycling. In addition, we show that ectopic expression of tll leads to brain tumors, in which Prospero, a key regulator of progenitor proliferation and differentiation, is suppressed whereas localization of molecular components involved in asymmetric Nb division is unaffected. These results as a whole uncover a distinct regulatory mechanism of self-renewal and differentiation of the MB progenitors that is different from the mechanisms found in other progenitors.
authors.affiliation: Structural Biology Center, National Institute of Genetics, and Department of Genetics, The Graduate University for Advanced Studies, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Kurusu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Adachi
authors.forename: Masataka
authors.initials: M
authors.lastname: Okabe
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Katsuo
authors.initials: K
authors.lastname: Furukubo-Tokunaga
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001932:Brain Neoplasms / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D024521:Mushroom Bodies / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C074090:TLL protein, Drosophila; D014157:Transcription Factors; C073099:pros protein, Drosophila