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Published February 4, 2022 | Supplemental Material + Published
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Brinker levels regulated by a promoter proximal element support germ cell homeostasis


A limited BMP signaling range in the stem cell niche of the ovary protects against germ cell tumors and promotes germ cell homeostasis. The canonical repressor of BMP signaling in both the Drosophila embryo and wing disc is the transcription factor Brinker (Brk), yet the expression and potential role of Brk in the germarium has not previously been described. Here, we find that brk expression requires a promoter-proximal element (PPE) to support long-distance enhancer action as well as to drive expression in the germarium. Furthermore, PPE subdomains have different activities; in particular, the proximal portion acts as a damper to regulate brk levels precisely. Using PPE mutants as well as tissue-specific RNA interference and overexpression, we show that altering brk expression within either the soma or the germline affects germ cell homeostasis. Remarkably, we find that Decapentaplegic (Dpp), the main BMP ligand and canonical antagonist of Brk, is upregulated by Brk in the escort cells of the germarium, demonstrating that Brk can positively regulate this pathway.

Additional Information

© 2022. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received 10 June 2021; Accepted 22 December 2021. We thank Gerard Campbel, Dorothea Godt and George Pyrowolakis for sharing fly stocks and antibodies, and Peiwei Chen for comments on the manuscript. Author contributions: Conceptualization: L.D., A.S.; Validation: L.D., S.N.; Formal analysis: L.D., S.N.; Investigation: L.D., S.N.; Resources: A.S.; Data curation: L.D., S.N.; Writing - original draft: L.D., S.N.; Writing - review & editing: L.D., S.N., A.S.; Visualization: L.D., S.N.; Supervision: A.S.; Project administration: A.S. This study was supported by funding from a National Institutes of Health grant (R03HD101961 to A.S.) and an American Cancer Society Postdoctoral Fellowship (PF-20-122-01 to S.N.). Open Access funding provided by the California Institute of Technology. Deposited in PMC for immediate release. Peer review history: The peer review history is available online at https://journals.biologists.com/dev/article-lookup/doi/10.1242/dev.199890. The authors declare no competing or financial interests.

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August 22, 2023
December 22, 2023