Peterson J S, Barkett M, McCall K
Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Dev Biol. 2003 Aug 1;260(1):113-23. doi: 10.1016/s0012-1606(03)00240-9.
In Drosophila oogenesis, the programmed cell death of germline cells occurs predominantly at three distinct stages. These cell deaths are subject to distinct regulatory controls, as cell death during early and midoogenesis is stress-induced, whereas the cell death of nurse cells in late oogenesis is developmentally regulated. In this report, we show that the effector caspase Drice is activated during cell death in both mid- and late oogenesis, but that the level and localization of activity differ depending on the stage. Active Drice formed localized aggregates during nurse cell death in late oogenesis; however, active Drice was found more ubiquitously and at a higher level during germline cell death in midoogenesis. Because Drice activity was limited in late oogenesis, we examined whether another effector caspase, Dcp-1, could drive the unique morphological events that occur normally in late oogenesis. We found that premature activation of the effector caspase, Dcp-1, resulted in a disappearance of filamentous actin, rather than the formation of actin bundles, suggesting that Dcp-1 activity must also be restrained in late oogenesis. Overexpression of the caspase inhibitor DIAP1 suppressed cell death induced by Dcp-1 but had no effect on cell death during late oogenesis. This limited caspase activation in dying nurse cells may prevent destruction of the nurse cell cytoskeleton and the connected oocyte.
在果蝇卵子发生过程中,生殖细胞的程序性细胞死亡主要发生在三个不同阶段。这些细胞死亡受到不同的调控,因为卵子发生早期和中期的细胞死亡是由应激诱导的,而卵子发生后期滋养细胞的细胞死亡则是受发育调控的。在本报告中,我们表明效应半胱天冬酶Drice在卵子发生中期和后期的细胞死亡过程中均被激活,但活性水平和定位因阶段而异。在卵子发生后期滋养细胞死亡期间,活性Drice形成局部聚集物;然而,在卵子发生中期生殖细胞死亡期间,活性Drice分布更广泛且水平更高。由于Drice活性在卵子发生后期受到限制,我们研究了另一种效应半胱天冬酶Dcp-1是否能驱动卵子发生后期正常发生的独特形态学事件。我们发现效应半胱天冬酶Dcp-1的过早激活导致丝状肌动蛋白消失,而不是形成肌动蛋白束,这表明Dcp-1的活性在卵子发生后期也必须受到抑制。半胱天冬酶抑制剂DIAP1的过表达抑制了Dcp-1诱导的细胞死亡,但对卵子发生后期的细胞死亡没有影响。垂死滋养细胞中这种有限的半胱天冬酶激活可能会防止滋养细胞细胞骨架和相连卵母细胞的破坏。