A conserved nuclear receptor, Tailless, is required for efficient proliferation and prolonged maintenance of mushroom body progenitors in the Drosophila brain.
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.
Kurusu
Mitsuhiko
M
Structural Biology Center, National Institute of Genetics, and Department of Genetics, The Graduate University for Advanced Studies, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Maruyama
Yasushi
Y
Adachi
Yoshitsugu
Y
Okabe
Masataka
M
Suzuki
Emiko
E
Furukubo-Tokunaga
Katsuo
K
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
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