Pipsqueak family genes dan/danr antagonize nuclear Pros to prevent neural stem cell aging in Drosophila larval brains.
Pipsqueak family genes dan/danr antagonize nuclear Pros to prevent neural stem cell aging in Drosophila larval brains.
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DOI：
10.3389/fnmol.2023.1160222
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发表时间：
2023
影响因子：
4.8
通讯作者：
Xi, Yongmei
中科院分区：
文献类型：
--
作者：
An, Huanping;Yu, Yue;Ren, Xuming;Zeng, Minghua;Bai, Yu;Liu, Tao;Zheng, Huimei;Sang, Rong;Zhang, Fan;Cai, Yu;Xi, Yongmei
神经干细胞衰老是神经发生中的一个基本问题。核内未成熟的Pros被认为是果蝇神经干细胞早期衰老的一个指标。神经干细胞如何防止过早的核Pros的潜在机制在很大程度上仍然未知。在这里，我们确定了两个pipsqueak家族基因，远端天线（dan）和远端天线相关（danr），促进神经干细胞（也称为神经母细胞，NB）在三龄幼虫大脑的增殖。在不存在Dan和Danr（dan/danr）的情况下，NB产生较少的具有较小谱系大小的子细胞。dan/danr克隆中的幼虫脑NBs显示核Prospero（Pros）的过早积累，其通常出现在蛹早期的终止NBs中。核内未成熟的Pros导致NB细胞周期缺陷和NB身份丢失。从dan/danr MARCM克隆中去除Pros可以防止谱系大小缩小并挽救NB标记的丢失。我们认为核Pros的时间是在WT终止NB中dan/danr下调之后。dan/danr和核Pros在NB中是相互排斥的。此外，dan/danr也需要晚时间调节器，Grainyhead（Grh），在三龄幼虫的大脑。我们的研究揭示了dan/danr在NBs细胞命运维持中的新功能。dan/danr拮抗果蝇幼虫脑中核Pros以防止NB老化。
Neural stem cell aging is a fundamental question in neurogenesis. Premature nuclear Pros is considered as an indicator of early neural stem cell aging in Drosophila. The underlying mechanism of how neural stem cells prevent premature nuclear Pros remains largely unknown. Here we identified that two pipsqueak family genes, distal antenna (dan) and distal antenna-related (danr), promote the proliferation of neural stem cells (also called neuroblasts, NBs) in third instar larval brains. In the absence of Dan and Danr (dan/danr), the NBs produce fewer daughter cells with smaller lineage sizes. The larval brain NBs in dan/danr clones show premature accumulation of nuclear Prospero (Pros), which usually appears in the terminating NBs at early pupal stage. The premature nuclear Pros leads to NBs cell cycle defects and NB identities loss. Removal of Pros from dan/danr MARCM clones prevents lineage size shrinkage and rescues the loss of NB markers. We propose that the timing of nuclear Pros is after the downregulation of dan/danr in the wt terminating NBs. dan/danr and nuclear Pros are mutually exclusive in NBs. In addition, dan/danr are also required for the late temporal regulator, Grainyhead (Grh), in third instar larval brains. Our study uncovers the novel function of dan/danr in NBs cell fate maintenance. dan/danr antagonize nuclear Pros to prevent NBs aging in Drosophila larval brains.
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影响因子：
64.5
作者：
Homem, Catarina C. F.;Steinmann, Victoria;Knoblich, Juergen A.
通讯作者：
Knoblich, Juergen A.
影响因子：
64.8
作者：
IkeshimaKataoka, H;Skeath, JB;Matsuzaki, F
通讯作者：
Matsuzaki, F
影响因子：
7.8
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Wu, Di;Wu, Litao;Yang, Xiaohang
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Yang, Xiaohang
影响因子：
9.8
作者：
Chai PC;Liu Z;Chia W;Cai Y
通讯作者：
Cai Y
影响因子：
2.7
作者：
Curtiss, Jennifer;Burnett, Micheal;Mlodzik, Marek
通讯作者：
Mlodzik, Marek