Steroid signaling in mature follicles is important for Drosophila ovulation
Edited by John J. Eppig, The Jackson Laboratory, Bar Harbor, ME, and approved December 19, 2016 (received for review August 29, 2016)
Significance
Ovulation is thought to be divergent from insects to mammals. In the latter case, ovulation is regulated by luteinizing hormone and the steroid hormone progesterone, neither of which is found in insects so far. This paper reports a role of ecdysteroids in Drosophila ovulation. Similar to the action of progesterone in mammals, 20-hydroxyecdysone produced in Drosophila follicle cells activates one of its receptors, EcR.B2, to allow proper activation of matrix metalloproteinase and follicle rupture. The conservation of steroid signaling in ovulation makes Drosophila a simple model to define the mechanism of steroid action in ovulation.
Abstract
Although ecdysteroid signaling regulates multiple steps in oogenesis, it is not known whether it regulates Drosophila ovulation, a process involving a matrix metalloproteinase-dependent follicle rupture. In this study, we demonstrated that ecdysteroid signaling is operating in mature follicle cells to control ovulation. Moreover, knocking down shade (shd), encoding the monooxygenase that converts ecdysone (E) to the more active 20-hydroxyecdysone (20E), specifically in mature follicle cells, blocked follicle rupture, which was rescued by ectopic expression of shd or exogenous 20E. In addition, disruption of the Ecdysone receptor (EcR) in mature follicle cells mimicked shd-knockdown defects, which were reversed by ectopic expression of EcR.B2 but not by EcR.A or EcR.B1 isoforms. Furthermore, we showed that ecdysteroid signaling is essential for the proper activation of matrix metalloproteinase 2 (Mmp2) for follicle rupture. Our data strongly suggest that 20E produced in follicle cells before ovulation activates EcR.B2 to prime mature follicles to be responsive to neuronal ovulatory stimuli, thus providing mechanistic insights into steroid signaling in Drosophila ovulation.
Acknowledgments
We thank Drs. Michael O’Connor, Allan Spradling, and Gerald Rubin for sharing fly lines and antibodies; the BDSC and the VDRC for fly stocks; the Developmental Study Hybridoma Bank for antibodies; anonymous reviewers for constructive comments; Drs. Joseph LoTurco, Karen Menuz, John Peluso, and Robert Gallo for valuable discussion on the manuscript; and Dr. Wei Li, Lylah Deady, and Wei Shen for technical support and discussion. J.S. is supported by the University of Connecticut Start-up fund and NIH/National Institute of Child Health and Human Development Grant R01-HD086175.
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Cover image: Pictured is an artist's rendering of reenergized adaptive cell transfer (ReACT), an immunotherapy strategy that combines a pathogen-based cancer vaccine and adaptive cell transfer approaches to treat solid tumors. Gang Xin et al. report that the ReACT strategy induced a robust antitumor T-cell response in mice with solid tumors. In treated mice, T cells migrated to tumor sites and eradicated primary tumors. Moreover, treated mice developed immunological protection to tumor recurrence. See the article by Xin et al. on pages 740–745. Image courtesy of Lin Zhang (Studio OY Design Consultancy, United Kingdom).
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Published online: January 9, 2017
Published in issue: January 24, 2017
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Acknowledgments
We thank Drs. Michael O’Connor, Allan Spradling, and Gerald Rubin for sharing fly lines and antibodies; the BDSC and the VDRC for fly stocks; the Developmental Study Hybridoma Bank for antibodies; anonymous reviewers for constructive comments; Drs. Joseph LoTurco, Karen Menuz, John Peluso, and Robert Gallo for valuable discussion on the manuscript; and Dr. Wei Li, Lylah Deady, and Wei Shen for technical support and discussion. J.S. is supported by the University of Connecticut Start-up fund and NIH/National Institute of Child Health and Human Development Grant R01-HD086175.
Notes
This article is a PNAS Direct Submission.
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The authors declare no conflict of interest.
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