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Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff

机译:Notch通过抑制Fez转录因子Earmuff的表达维持果蝇II型成神经细胞

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摘要

Notch signaling is crucial for maintaining neural stem cell (NSC) self-renewal and heterogeneity; however, the underlying mechanism is not well understood. In Drosophila, loss of Notch prematurely terminates the self-renewal of larval type II neuroblasts (NBs, the Drosophila NSCs) and transforms type II NBs into type I NBs. Here, we demonstrate that Notch maintains type II NBs by suppressing the activation of earmuff (erm) by Pointed P1 (PntP1). We show that loss of Notch or components of its canonical pathway leads to PntP1-dependent ectopic Erm expression in type II NBs. Knockdown of Erm significantly rescues the loss-of-Notch phenotypes, and misexpression of Erm phenocopies the loss of Notch. Ectopically expressed Erm promotes the transformation of type II NBs into type I NBs by inhibiting PntP1 function and expression in type II NBs. Our work not only elucidates a key mechanism of Notch-mediated maintenance of type II NB self-renewal and identity, but also reveals a novel function of Erm.
机译:Notch信号对于维持神经干细胞(NSC)的自我更新和异质性至关重要。但是,底层机制尚不为人所知。在果蝇中,Notch的丧失会提前终止幼虫II型成神经细胞(NB,果蝇NSC)的自我更新,并将II型NB转变为I型NB。在这里,我们证明Notch通过抑制由尖的P1(PntP1)激活的耳罩(erm)来维持II型NB。我们显示,Notch或其规范途径的组成部分的丢失导致II型NBs中依赖PntP1的异位Erm表达。击倒Erm可以显着挽救Notch缺失的表型,而Erm表型的错误表达可以复制Notch的缺失。异位表达的Erm通过抑制PntP1功能和II型NBs中的表达来促进II型NBs向I型NBs的转化。我们的工作不仅阐明了Notch介导的II型NB自我更新和识别的关键机制,而且还揭示了Erm的新功能。

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