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Physiological apoptosis of polar cells during Drosophila oogenesis is mediated by Hid-dependent regulation of Diap1.

机译:果蝇卵子发生过程中极性细胞的生理凋亡是由Diap1的Hid依赖性调节介导的。

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Although much has been learned in recent years about the apoptotic machinery, the mechanisms underlying survival and death choices during development of metazoans remain less clearly understood. During early oogenesis in Drosophila, a small excess in the number of specialized somatic cells, called polar cells (PCs), produced at follicle extremities is reduced to exactly two cells through apoptosis by mid-oogenesis. We have found that PCs destined to die first lose their apical contacts and then round up and shrink progressively until they disappear. Caspases are activated only once the cells have begun to shrink, suggesting that they are implicated in this part of the process, but not in the initial loss of cell polarity. Loss-of-function analyses based on mutant, clonal and RNAi approaches show that among the RHG family of pro-apoptotic factors, Hid is specifically necessary for PC apoptosis, as well as the initiator caspase Dronc and its adaptor Dark/Apaf-1, and likely several effector caspases, in particular Drice. In addition, we show that Hid protein and transcripts accumulate specifically in PCs destined to die, while the anti-apoptotic factor Diap1 is downregulated in these cells in a hid-dependent manner. Therefore, our results implicate the Hid-Diap1 module as an important regulatory point in a developmental case of apoptosis.
机译:尽管近年来有关凋亡机制的知识很多,但对后生动物发育过程中生存和死亡选择的潜在机制仍知之甚少。在果蝇的早期卵子发生过程中,卵泡末端产生的称为极性细胞(PCs)的专门体细胞的数量略有过量,通过卵中生发生的凋亡将其减少为恰好两个细胞。我们发现,注定要死亡的PC会先失去根尖接触,然后向上舍入并逐渐收缩直到消失。胱天蛋白酶只有在细胞开始萎缩后才被激活,这表明它们参与了该过程的这一部分,但与细胞极性的最初丧失无关。基于突变,克隆和RNAi方法的功能丧失分析表明,在RHG促凋亡因子家族中,Hid对PC凋亡以及启动子胱天蛋白酶Dronc及其衔接子Dark / Apaf-1特别重要,可能还有几个效应胱天蛋白酶,尤其是Drice。此外,我们表明,Hid蛋白和转录本在死于PC的细胞中特别积累,而抗凋亡因子Diap1在这些细胞中以hid依赖性方式下调。因此,我们的结果表明,Hid-Diap1模块是细胞凋亡发展中的重要调控点。

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