Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary

Jung, L. E.; Warren, A. I.; Yin, C.; Huang, W.; Simmons, A. C.; McDonald, S. I.; Swain, L. A.; Garrido, V. E.; Phipps, D. N.; Cesar, B.; Finger, D. S.; Sun, Z.; Nystul, T.; Ables, E. T.

doi:10.64898/2025.12.19.695538

bioRxiv · 10.64898/2025.12.19.695538

Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary

Jung, L. E.·Warren, A. I.·Yin, C.·Huang, W.·Simmons, A. C.·McDonald, S. I.·Swain, L. A.·Garrido, V. E.·Phipps, D. N.·Cesar, B.·Finger, D. S.·Sun, Z.·Nystul, T.·Ables, E. T.

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Abstract

In the Drosophila ovary, the steroid hormone ecdysone controls germline stem cell (GSC) maintenance and germ cell differentiation. Prior studies demonstrated that ecdysone regulates germ cell differentiation non-autonomously via the nuclear receptor Ecdysone Receptor (EcR) in ovarian somatic cells. Although EcR is also expressed in GSCs and their differentiating daughters, potential direct roles for EcR in GSCs independent of the soma have not been examined. Here, we demonstrate that EcR functions autonomously in GSCs and cystoblasts to control germline differentiation. While depletion of EcR from GSCs mildly reduces GSC self-renewal, over-expression of EcR specifically in GSCs and cystoblasts impedes germ cell differentiation, phenotypically resembling bag of marbles loss-of-function and Bone Morphogenetic Protein signaling constitutive activation. We propose that while low levels of EcR are essential to maintain GSC self-renewal and permit initial differentiation, higher levels of EcR accumulate in differentiated germ cells to promote transcription of maternal genes, providing temporal control over germline differentiation. These data support the model that stem cells harbor unique mechanisms to integrate signals from multiple cell sources that safeguard their self-renewal in response to local and physiological cues. SUMMARY STATEMENTThe nuclear receptor EcR modulates stem cell maintenance and differentiation in ovarian germ cells.

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Jung, L. E., Warren, A. I., Yin, C., Huang, W., Simmons, A. C., McDonald, S. I., Swain, L. A., Garrido, V. E., Phipps, D. N., Cesar, B., Finger, D. S., Sun, Z., Nystul, T., Ables, E. T.. 2025-12-22. Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary. https://doi.org/10.64898/2025.12.19.695538

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