Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells
Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells
复制标题
DOI：
10.1073/pnas.94.10.5131
复制
发表时间：
1997-05-13
影响因子：
11.1
通讯作者：
Nambu, JR
中科院分区：
文献类型：
--
作者：
Zhou, L;Schnitzler, A;Nambu, JR
在果蝇中，染色体区域75C1-2至少包含三个基因，即Reaper(RPR)、Head Insion Defect(HID)和Grim，它们在激活细胞程序性死亡过程中具有重要功能。为了更好地了解这些基因是如何杀死细胞的，我们利用了一组定义良好的胚胎中枢神经系统中线细胞，这些细胞通常表现出特定的胶质细胞死亡模式。在这项研究中，我们证明了RPR和HID在死亡的中线细胞中都有表达，并且正常的中线细胞死亡模式需要75C1-2区间的多个基因的功能。我们还利用P[UAS]/P[Gal4]系统将RPR和HID的表达靶向到中线细胞。单独靶向表达RPR或HID不足以诱导异位中线细胞死亡。然而，RPR和HID的共同表达迅速诱导了异位中线细胞死亡，导致了中线细胞发育异常的突变体特有的轴突支架缺陷。中线靶向表达杆状病毒p35蛋白是一种半胱氨酸天冬氨酸氨基转移酶抑制剂，可以阻止正常和异位RPR和HID诱导的细胞死亡。综上所述，我们的结果表明，RPR和HID共同表达，并在中枢神经系统中线发育过程中协同诱导细胞程序性死亡。
In Drosophila, the chromosomal region 75C1-2 contains at least three genes, reaper (rpr), head involution defective (hid), and grim, that have important functions in the activation of programmed cell death. To better understand how cells are killed by these genes, we have utilized a well defined set of embryonic central nervous system midline cells that normally exhibit a specific pattern of glial cell death. In this study we show that both rpr and hid are expressed in dying midline cells and that the normal pattern of midline cell death requires the function of multiple genes in the 75C1-2 interval. We also utilized the P[UAS]/P[Gal4] system to target expression of rpr and hid to midline cells. Targeted expression of rpr or hid alone was not sufficient to induce ectopic midline cell death. However, expression of both rpr and hid together rapidly induced ectopic midline cell death that resulted in axon scaffold defects characteristic of mutants with abnormal midline cell development. Midline-targeted expression of the baculovirus p35 protein, a caspase inhibitor, blocked both normal and ectopic rpr- and hid-induced cell death. Taken together, our results suggest that rpr and hid are expressed together and cooperate to induce programmed cell death during development of the central nervous system midline.