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Updated: Jul 15, 2025
Methods to Test Endocrine Disruption in Drosophila melanogaster
Published on: July 3, 2019
The Drosophila ecdysone receptor promotes or suppresses proliferation according to ligand level
Gantas Perez-Mockus1, Luca Cocconi1, Cyrille Alexandre1
1The Francis Crick Institute, London NW1 1AT, UK.
Abstract:
The steroid hormone 20-hydroxy-ecdysone (20E) promotes proliferation in Drosophila wing precursors at low titer but triggers proliferation arrest at high doses. Remarkably, wing precursors proliferate normally in the complete absence of the 20E receptor, suggesting that low-level 20E promotes proliferation by overriding the default anti-proliferative activity of the receptor. By contrast, 20E needs its receptor to arrest proliferation. Dose-response RNA sequencing (RNA-seq) analysis of ex vivo cultured wing precursors identifies genes that are quantitatively activated by 20E across the physiological range, likely comprising positive modulators of proliferation and other genes that are only activated at high doses. We suggest that some of these "high-threshold" genes dominantly suppress the activity of the pro-proliferation genes. We then show mathematically and with synthetic reporters that combinations of basic regulatory elements can recapitulate the behavior of both types of target genes. Thus, a relatively simple genetic circuit can account for the bimodal activity of this hormone.
Insights
The steroid hormone 20-hydroxyecdysone (20E) has dual roles in Drosophila wing development. Low doses promote cell proliferation, while high doses arrest it, mediated by a simple genetic circuit.
Area of Science:
- Developmental Biology
- Molecular Endocrinology
- Genetics
Background:
- The steroid hormone 20-hydroxyecdysone (20E) plays a critical role in insect development.
- Its precise function in regulating cell proliferation, particularly in imaginal discs like wing precursors, is complex and dose-dependent.
Purpose of the Study:
- To elucidate the dose-dependent effects of 20E on Drosophila wing precursor proliferation.
- To identify the molecular mechanisms and genetic circuits underlying 20E's bimodal activity.
Main Methods:
- Dose-response RNA sequencing (RNA-seq) of ex vivo cultured Drosophila wing precursors.
- Mathematical modeling and synthetic reporter assays to analyze gene regulation.
Main Results:
- Low-titer 20E promotes proliferation, potentially by overriding the receptor's default anti-proliferative activity.
- High-titer 20E arrests proliferation, requiring the 20E receptor.
- RNA-seq identified genes activated quantitatively by 20E, including pro-proliferation and high-threshold suppressors.
Conclusions:
- A simple genetic circuit with basic regulatory elements can explain the bimodal activity of 20E.
- This circuit involves genes with different activation thresholds, mediating both proliferation and arrest.
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