Bass B Paige, Cullen Kristen, McCall Kimberly
Molecular Biology, Cell Biology and Biochemistry Program, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Dev Biol. 2007 Apr 15;304(2):771-85. doi: 10.1016/j.ydbio.2007.01.029. Epub 2007 Jan 25.
longitudinals-lacking (lola) was identified in Drosophila as a gene encoding several alternatively spliced transcription factors involved in axon guidance. Here we report that lola also plays a critical role in programmed cell death in the ovary. lola mutant germline clones show a high percentage of egg chambers with nurse cell nuclei persisting past stage 13, indicating a block in developmental nurse cell death. Mutants also show a disruption in the induced programmed cell death that occurs during mid-oogenesis in response to starvation. Further characterization revealed that lola germline clones exhibit abnormal nuclear organization which becomes increasingly severe with age. Chromatin appears diffuse and fails to condense properly or undergo DNA fragmentation in dying nurse cells. Masses of nuclear material accumulate in the ovaries of older flies containing lola germline clones. We propose that lola is necessary for complete chromatin condensation which occurs during programmed cell death in the ovary. Alleles differed in the strength of their phenotypes but interestingly, the severity of their ovarian phenotypes was independent of the strength of their neuronal phenotypes, suggesting a differential requirement for individual lola isoforms in the ovary and nervous system.
在果蝇中发现的“纵向缺失”（lola）基因编码几种参与轴突导向的可变剪接转录因子。在此我们报告，lola在卵巢程序性细胞死亡中也起着关键作用。lola突变种系克隆显示，有很高比例的卵室中，滋养细胞核持续存在到13期之后，这表明发育中的滋养细胞死亡受阻。突变体还显示，在卵子发生中期因饥饿诱导的程序性细胞死亡出现紊乱。进一步的特征分析表明，lola种系克隆表现出异常的核组织，且随着年龄增长愈发严重。在即将死亡的滋养细胞中，染色质显得弥散，无法正常凝聚或发生DNA片段化。在含有lola种系克隆的老龄果蝇卵巢中，核物质大量积聚。我们认为，lola对于卵巢程序性细胞死亡过程中发生的完全染色质凝聚是必需的。等位基因在表型强度上存在差异，但有趣的是，其卵巢表型的严重程度与神经表型的强度无关，这表明卵巢和神经系统对单个lola亚型有不同的需求。
