Hensey C, Gautier J
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Mech Dev. 1997 Dec;69(1-2):183-95. doi: 10.1016/s0925-4773(97)00191-3.
Recent work identified an apoptotic program in gastrulation stage Xenopus embryos (Anderson, J.A., Lewellyn, A.L., Maller, J.L., 1997. Mol. Biol. Cell 8, 1195-1206; Stack, J.H., Newport, J.W., 1997. Development 124, 3185-3195). Here, we characterize in detail this maternal cell death program, which is set up at fertilization and abruptly activated at the onset of gastrulation, following DNA damage or treatment of embryos with inhibitors of transcription, translation, or replication, between the time of fertilization and the midblastula transition (MBT). This apoptotic pathway is activated under tightly regulated developmental control(s): if the same treatments are applied after the MBT the apoptotic response is abrogated. Embryos displayed many characteristic apoptotic features, including DNA fragmentation, caspase activation, and embryonic death was blocked in vivo by the ectopic expression of Bcl-2, or injection of the caspase-3 inhibitor z-DEVD-fmk. The precise timing and the execution of this maternal cell death program is set at fertilization and does not depend on the type of stress applied, on cell cycle progression, or on de novo protein synthesis. This maternal developmental program might palliate the lack of cell cycle checkpoints in the pre-MBT embryo.
近期研究在原肠胚形成阶段的非洲爪蟾胚胎中发现了一种凋亡程序(Anderson, J.A., Lewellyn, A.L., Maller, J.L., 1997. 《分子生物学与细胞》8, 1195 - 1206; Stack, J.H., Newport, J.W., 1997. 《发育》124, 3185 - 3195)。在此,我们详细描述了这种母源细胞死亡程序,它在受精时建立,并在原肠胚形成开始时突然激活,在受精至中囊胚转换(MBT)期间,胚胎受到DNA损伤或用转录、翻译或复制抑制剂处理后会激活该程序。这种凋亡途径是在严格调控的发育控制下被激活的:如果在MBT之后进行相同的处理,凋亡反应则会被消除。胚胎表现出许多典型的凋亡特征,包括DNA片段化、半胱天冬酶激活,并且在体内,通过异位表达Bcl - 2或注射半胱天冬酶 - 3抑制剂z - DEVD - fmk可阻断胚胎死亡。这种母源细胞死亡程序的确切时间和执行在受精时就已设定,并且不依赖于所施加的应激类型、细胞周期进程或从头蛋白质合成。这种母源发育程序可能弥补了MBT前胚胎中细胞周期检查点的缺失。