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Two-factor specification of apoptosis: TGF-β signaling acts cooperatively with ecdysone signaling to induce cell- and stage-specific apoptosis of larval neurons during metamorphosis in Drosophila melanogaster.
Apoptosis ( IF 6.1 ) Pub Date : 2019-12-01 , DOI: 10.1007/s10495-019-01574-4
Zixing Wang 1 , Gyunghee Lee 2 , Richard Vuong 3 , Jae H Park 1, 2
Affiliation  

Developmentally regulated programmed cell death (PCD) is one of the key cellular events for precise controlling of neuronal population during postembryonic development of the central nervous system. Previously we have shown that a group of corazonin-producing peptidergic neurons (vCrz) undergo apoptosis in response to ecdysone signaling via ecdysone receptor (EcR)-B isoforms and Ultraspiracle during early phase of metamorphosis. Further utilizing genetic, transgenic, and mosaic analyses, we have found that TGF-β signaling mediated by a glia-produced ligand, Myoglianin, type-I receptor Baboon (particularly Babo-A isoform) and dSmad2, is also required autonomously for PCD of the vCrz neurons. Our studies show that TGF-β signaling is not acting epistatically to EcR or vice versa. We also show that ectopic expression of a constitutively active phosphomimetic form of dSmad2 (dSmad2PM) is capable of inducing premature death of vCrz neurons in larva but not other larval neurons. Intriguingly, the dSmad2PM-mediated killing is completely suppressed by coexpression of a dominant-negative form of EcR (EcRDN), suggesting that EcR function is required for the proapoptotic dSmad2PM function. Based on these data, we suggest that TGF-β and ecdysone signaling pathways act cooperatively to induce vCrz neuronal PCD. We propose that this type of two-factor authentication is a key developmental strategy to ensure the timely PCD of specific larval neurons during metamorphosis.

中文翻译:

凋亡的两因素说明:TGF-β信号传导与蜕皮激素信号传导协同作用,在果蝇变态过程中诱导幼虫神经元的细胞和阶段特异性凋亡。

发育调控的程序性细胞死亡(PCD)是在中枢神经系统胚后发育过程中精确控制神经元种群的关键细胞事件之一。以前我们已经表明,在变态的早期阶段,一组产生corazonin的肽能神经元(vCrz)通过蜕皮激素受体(EcR)-B同工型和Ultraspiracle响应蜕皮激素信号传导而发生凋亡。进一步利用遗传,转基因和镶嵌分析,我们发现由胶质细胞产生的配体,Myoglianin,I型受体狒狒(尤其是Babo-A同工型)和dSmad2介导的TGF-β信号传导也是PCD的自主需要vCrz神经元。我们的研究表明,TGF-β信号传导并不对EcR起作用,反之亦然。我们还显示dSmad2(dSmad2PM)的组成型活性磷酸化形式的异位表达能够诱导幼虫中vCrz神经元的过早死亡,但不能诱导其他幼虫神经元的过早死亡。有趣的是,共显性阴性形式的EcR(EcRDN)共表达可完全抑制dSmad2PM介导的杀伤,提示促凋亡dSmad2PM功能需要EcR功能。基于这些数据,我们建议TGF-β和蜕皮激素信号通路协同作用,以诱导vCrz神经元PCD。我们建议这种类型的两因素身份验证是一种重要的发展策略,可确保在变态期间特定幼虫神经元的及时PCD。dSmad2PM介导的杀伤作用通过显性阴性形式的EcR(EcRDN)的共表达被完全抑制,这提示促凋亡dSmad2PM功能需要EcR功能。基于这些数据,我们建议TGF-β和蜕皮激素信号通路协同作用,以诱导vCrz神经元PCD。我们建议这种类型的两因素身份验证是一种重要的发展策略,可确保在变态期间特定幼虫神经元的及时PCD。dSmad2PM介导的杀伤作用通过显性阴性形式的EcR(EcRDN)的共表达被完全抑制,这提示促凋亡dSmad2PM功能需要EcR功能。基于这些数据,我们建议TGF-β和蜕皮激素信号通路协同作用,以诱导vCrz神经元PCD。我们建议这种类型的两因素身份验证是一种重要的发展策略,可确保在变态期间特定幼虫神经元的及时PCD。
更新日期:2019-11-01
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