Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
Cell Death Differ. 2010 Nov;17(11):1717-27. doi: 10.1038/cdd.2010.49. Epub 2010 May 7.
We show here that similar to starvation, ingestion of the bacterial product rapamycin (RAP) interferes with egg production in female Drosophila. RAP ingestion results in posterior follicle cells (PFC) in stage 8/9 egg chambers losing epithelial polarity, after which PFC invade and phagocytose the oocyte. Nurse cell apoptosis then occurs, followed by total egg chamber destruction. Knockdown of the RAP receptor FKBP12 specifically in PFC rescues oogenesis and also the laying of embryos that develop into normal offspring in flies fed RAP. Thus, somatic cells can be induced to destroy intact oocytes without a requirement for earlier oocyte compromise. Genes that control apicobasal epithelial polarity were found to be involved in egg chamber destruction. In flies bearing heterozygous mutations for discs large, merlin, or warts, PFC epithelia fail to lose polarity on RAP treatment. Embryo laying and offspring development to adulthood are rescued in all of these mutants when housed on RAP concentrations that block oogenesis in wild-type flies. The response to RAP was found to be conserved in mammals, as mouse ovarian follicles cultured in vitro with RAP show the rapid destruction of the oocyte by adjacent granulosa cells. Inducible somatic oocyte destruction is thus implicated in controlling egg survival in insects and mammals.
我们在这里表明，类似于饥饿，摄入细菌产物雷帕霉素（RAP）会干扰雌性果蝇的产卵。RAP 的摄入导致第 8/9 期卵囊中后滤泡细胞（PFC）失去上皮极性，之后 PFC 侵入并吞噬卵母细胞。随后发生滋养细胞凋亡，然后整个卵室被破坏。特异性敲低 PFC 中的 RAP 受体 FKBP12 可挽救卵子发生，也可挽救在喂食 RAP 的果蝇中发育成正常后代的胚胎。因此，体细胞可以被诱导破坏完整的卵母细胞，而不需要早期卵母细胞受损。控制顶端基底上皮极性的基因被发现参与卵室破坏。在携带 discslarge、merlin 或warts 杂合突变的果蝇中，RAP 处理后 PFC 上皮细胞未能失去极性。当这些突变体在阻止野生型果蝇卵子发生的 RAP 浓度下饲养时，产卵和后代发育到成年都得到挽救。在体外用 RAP 培养的小鼠卵巢卵泡中也发现了 RAP 的反应是保守的，表明相邻的颗粒细胞迅速破坏卵母细胞。因此，诱导性体卵母细胞破坏被认为参与控制昆虫和哺乳动物的卵子存活。
