Programmed cell death mechanisms of identifiable peptidergic neurons in Drosophila melanogaster
Programmed cell death mechanisms of identifiable peptidergic neurons in Drosophila melanogaster
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DOI：
10.1242/dev.02376
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发表时间：
2006-06-01
期刊：
影响因子：
4.6
通讯作者：
Park, Jae H.
中科院分区：
文献类型：
--
作者：
Choi, Youn-Jeong;Lee, Gyunghee;Park, Jae H.
在果蝇中枢神经系统(CNS)发育的早期，神经元程序性细胞死亡(PCD)的分子基础很大程度上是未知的，部分原因是缺乏合适的模型系统。在这里，我们提供的证据表明，在幼虫中枢神经系统的腹神经索中表达神经肽Corazin(CRZ)基因的一组神经元(VCrz)在变态开始后6小时内发生程序性死亡。Caspase抑制剂p35的靶向表达阻止了死亡，这表明这些幼虫神经元是通过caspase依赖的途径被消除的。涉及蜕皮激素受体-B(ECR-B)亚型的蜕皮激素信号转导的遗传和转基因中断可抑制vCrz死亡，而将ECR-B1或ECR-B2亚型转基因重新导入ECR-B缺失突变体可恢复正常死亡。在收割机缺失突变体中，收割机在vCrz神经元中的表达和对vCrz细胞死亡的抑制表明收割机功能是死亡所必需的，而没有发现HID或GRIM作为死亡促进剂的明显作用。我们的数据进一步表明，diap1不是vCrz神经元PCD的中枢调节因子。在缺乏Dronc或暗功能的突变体中观察到vCrz-细胞死亡的显著延迟，表明凋亡体的形成是及时执行死亡所必需的，但不是充分的。这些结果表明，在变态早期，被激活的蜕皮激素信号决定了神经元退化的精确发育时间，随后收割者介导的caspase激活通过一条新的DIAP1非依赖性途径发生。
The molecular basis of programmed cell death ( PCD) of neurons during early metamorphic development of the central nervous system ( CNS) in Drosophila melanogaster are largely unknown, in part owing to the lack of appropriate model systems. Here, we provide evidence showing that a group of neurons ( vCrz) that express neuropeptide Corazonin ( Crz) gene in the ventral nerve cord of the larval CNS undergo programmed death within 6 hours of the onset of metamorphosis. The death was prevented by targeted expression of caspase inhibitor p35, suggesting that these larval neurons are eliminated via a caspase-dependent pathway. Genetic and transgenic disruptions of ecdysone signal transduction involving ecdysone receptor-B ( EcR-B) isoforms suppressed vCrz death, whereas transgenic re-introduction of either EcR-B1 or EcR-B2 isoform into the EcR-B-null mutant resumed normal death. Expression of reaper in vCrz neurons and suppression of vCrz-cell death in a reaper-null mutant suggest that reaper functions are required for the death, while no apparent role was found for hid or grim as a death promoter. Our data further suggest that diap1 does not play a role as a central regulator of the PCD of vCrz neurons. Significant delay of vCrz-cell death was observed in mutants that lack dronc or dark functions, indicating that formation of an apoptosome is necessary, but not sufficient, for timely execution of the death. These results suggest that activated ecdysone signaling determines precise developmental timing of the neuronal degeneration during early metamorphosis, and that subsequent reaper-mediated caspase activation occurs through a novel DIAP1-independent pathway.