The Francis Crick Institute
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The Drosophila ecdysone receptor promotes or suppresses proliferation according to ligand level.

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journal contribution
posted on 2023-10-26, 09:41 authored by Gantas Perez-Mockus, Luca Cocconi, Cyrille Alexandre, Birgit Aerne, Guillaume Salbreux, Jean-Paul Vincent
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.


Crick (Grant ID: CC2072, Grant title: Vincent CC2072) Crick (Grant ID: CC2062, Grant title: Salbreux CC2062) Wellcome Trust (Grant ID: 206341/Z/17/Z, Grant title: WT 206341/Z/17/Z) Crick (Grant ID: CC2138, Grant title: Tapon CC2138)