Local initiation of caspase activation in Drosophila salivary gland programmed cell death in vivo
Local initiation of caspase activation in Drosophila salivary gland programmed cell death in vivo
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DOI：
10.1073/pnas.0702733104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Miura, Masayuki
中科院分区：
文献类型：
--
作者：
Takemoto, Kiwamu;Kuranaga, Erina;Miura, Masayuki
细胞程序性死亡或凋亡是动物发育过程中的一个重要事件。在体内caspase激活的时空分析可以提供新的见解程序性细胞死亡发生在发展过程中。在这里，使用FRET为基础的caspase-3的指示剂，SCAT 3，我们报告的结果，在体内发育果蝇caspase激活的实时成像分析。在果蝇中，唾液腺是由半胱天冬酶介导的程序性细胞死亡所雕刻的，该程序性细胞死亡由类固醇激素20-羟基蜕皮激素（ecdysone）启动。使用SCAT 3探针，我们观察到，在唾液腺中的半胱天冬酶激活开始于前部细胞，然后在体内繁殖到后部细胞。体外唾液腺培养实验表明，蜕皮激素局部暴露于前唾液腺再现了体内观察到的半胱天冬酶激活梯度。在β FTZ-F1突变体中，半胱天冬酶激活被延迟，并在体内以随机模式发生。与体内反应相反，β FTZ-F1突变体的唾液腺对蜕皮激素表现出正常的体外反应，表明β FTZ-F1可能参与蜕皮激素的生物合成和从环腺分泌蜕皮激素，用于局部启动程序性细胞死亡。这些结果暗示了β FTZ-F1在协调发育中唾液腺细胞凋亡的启动中的作用。
Programmed cell death, or apoptosis, is an essential event in animal development. Spatiotemporal analysis of caspase activation in vivo could provide new insights into programmed cell death occurring during development. Here, using the FRET-based caspase-3 indicator, SCAT3, we report the results of live-imaging analysis of caspase activation in developing Drosophila in vivo. In Drosophila, the salivary gland is sculpted by caspase-mediated programmed cell death initiated by the steroid hormone 20-hydroxyecdysone (ecdysone). Using a SCAT3 probe, we observed that caspase activation in the salivary glands begins in the anterior cells and is then propagated to the posterior cells in vivo. In vitro salivary gland culture experiments indicated that local exposure of ecdysone to the anterior salivary gland reproduces the caspase activation gradient as observed in vivo. In beta FTZ-F1 mutants, caspase activation was delayed and occurred in a random pattern in vivo. In contrast to the in vivo response, the salivary glands from beta FTZ-F1 mutants showed a normal in vitro response to ecdysone, suggesting that beta FTZ-F1 may be involved in ecdysteroid biosynthesis and secretion of ecdysone from the ring gland for local initiation of programmed cell death. These results imply a role of beta FTZ-F1 in coordinating the initiation of salivary gland apoptosis in development.