Phantom, a cytochrome P450 enzyme essential for ecdysone biosynthesis, plays a critical role in the control of border cell migration in Drosophila

Abstract

Summary The border cells of Drosophila are a model system for coordinated cell migration. Ecdysone signaling has been shown to act as the timing signal to initiate the migration process. Here we find that mutations in phantom (phm), encoding an enzyme in the ecdysone biosynthesis pathway, block border cell migration when the entire follicular epithelium of an egg chamber is mutant, even when the associated germline cells (nurse cells and oocyte) are wildtype. Conversely, mutant germline cells survive and do not affect border cell migration, as long as the surrounding follicle cells are wildtype. Interestingly, even small patches of wildtype follicle cells in a mosaic epithelium are sufficient to allow the production of above-threshold levels of ecdysone to promote border cell migration. The same phenotype is observed with mutations in shade (shd), encoding the last enzyme in the pathway that converts ecdysone to the active 20-hydroxyecdysone. Administration of high 20-hydroxyecdysone titers in the medium can also rescue the border cell migration phenotype in cultured egg chambers with an entirely phm mutant follicular epithelium. These results indicate that in normal oogenesis, the follicle cell epithelium of each individual egg chamber must supply sufficient ecdysone precursors, leading ultimately to high enough levels of mature 20-hydroxyecdysone to the border cells to initiate their migration. Neither the germline, nor the neighboring egg chambers, nor the surrounding hemolymph appear to provide threshold amounts of 20-hydroxyecdysone to do so. This “egg chamber autonomous” ecdysone synthesis constitutes a useful way to regulate the individual maturation of the asynchronous egg chambers present in the Drosophila ovary.

Steroid signaling in mature follicles is important for Drosophila ovulation

“…This hypothesis is consistent with the finding that the ligand sensor for ecdysteroids shows a stage-specific activity including stage 10 and stage 14 (32,33). This notion is further supported by this study that up-regulation of Shd in mature follicle cells produces 20E to regulate ovulation and a previous study that local ecdysteroids produced in follicle cells regulate border cell migration (37).…”

“…Ecdysteroids have long been known to play essential roles in developmental transitions, such as larval molting and metamorphosis (27,28). In contrast, the roles of ecdysteroids in adult physiology have just started to emerge (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

Steroid Signaling Establishes a Female Metabolic State and Regulates SREBP to Control Oocyte Lipid Accumulation

“…EcR and downstream components of the ecdysone-signaling pathway are genetically required for oocyte development [23][24][25]. Moreover, a recent study has shown that ecdysone produced from the somatic follicle cells is required for border cell migration during stage 9 of oogenesis [26]. However, the importance of EcR in nutrient storage during late stages of egg development has not been defined.…”

Ovarian ecdysteroid biosynthesis and female germline stem cells

“…9 In addition, certain genes encoding the ecdysteroidogenic enzymes are required for egg development after stage 8, 19,26 egg production, 30 and border cell migration. 31 It is well-documented that, for the regulation of molting and metamorphosis, the biosynthesis and signaling of ecdysteroids are coordinately modulated in response to various environmental cues such as nutrition, photoperiod, and temperature. 32,33 Therefore, it is possible that the environmental cues are also reflected in egg production processes such as in the control of GSC number.…”