Inducible somatic oocyte destruction in response to rapamycin requires wild-type regulation of follicle cell epithelial polarity.
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.
Thomson
T C
TC
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
Johnson
J
J
D000818:Animals; D017209:Apoptosis; D016764:Cell Polarity / Q000187:drug effects; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005496:Follicular Atresia; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D009866:Oogenesis / Q000187:drug effects* / Q000502:physiology; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D013217:Starvation
D029721:Drosophila Proteins; D020123:Sirolimus