TY - JOUR
T1 - Steroid signaling promotes stem cell maintenance in the Drosophila testis.
AU - Li, Yijie
AU - Ma, Qing
AU - Cherry, Christopher M.
AU - Matunis, Erika L.
N1 - Funding Information:
We thank D. Drummond-Barbosa, P. Espenshade, J. Boeke, E. Chen, D. Montell, C. Thummel, H. Krause, C. Dauphin-Villemant, M. Jindra, H. Sun, P. Badenhorst, K. Howard, M. Issigonis, R. Stine, the Bloomington Drosophila Stock Center, and the Vienna Drosophila RNAi Center for flies, antibodies, and advice, and M. de Cuevas for editing the paper. This work was supported by NIH grants HD040307 HD052937 (E.M.).
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Stem cell regulation by local signals is intensely studied, but less is known about the effects of hormonal signals on stem cells. In Drosophila, the primary steroid twenty-hydroxyecdysone (20E) regulates ovarian germline stem cells (GSCs) but was considered dispensable for testis GSC maintenance. Male GSCs reside in a microenvironment (niche) generated by somatic hub cells and adjacent cyst stem cells (CySCs). Here, we show that depletion of 20E from adult males by overexpressing a dominant negative form of the Ecdysone receptor (EcR) or its heterodimeric partner ultraspiracle (usp) causes GSC and CySC loss that is rescued by 20E feeding, uncovering a requirement for 20E in stem cell maintenance. EcR and USP are expressed, activated and autonomously required in the CySC lineage to promote CySC maintenance, as are downstream genes ftz-f1 and E75. In contrast, GSCs non-autonomously require ecdysone signaling. Global inactivation of EcR increases cell death in the testis that is rescued by expression of EcR-B2 in the CySC lineage, indicating that ecdysone signaling supports stem cell viability primarily through a specific receptor isoform. Finally, EcR genetically interacts with the NURF chromatin-remodeling complex, which we previously showed maintains CySCs. Thus, although 20E levels are lower in males than females, ecdysone signaling acts through distinct cell types and effectors to ensure both ovarian and testis stem cell maintenance.
AB - Stem cell regulation by local signals is intensely studied, but less is known about the effects of hormonal signals on stem cells. In Drosophila, the primary steroid twenty-hydroxyecdysone (20E) regulates ovarian germline stem cells (GSCs) but was considered dispensable for testis GSC maintenance. Male GSCs reside in a microenvironment (niche) generated by somatic hub cells and adjacent cyst stem cells (CySCs). Here, we show that depletion of 20E from adult males by overexpressing a dominant negative form of the Ecdysone receptor (EcR) or its heterodimeric partner ultraspiracle (usp) causes GSC and CySC loss that is rescued by 20E feeding, uncovering a requirement for 20E in stem cell maintenance. EcR and USP are expressed, activated and autonomously required in the CySC lineage to promote CySC maintenance, as are downstream genes ftz-f1 and E75. In contrast, GSCs non-autonomously require ecdysone signaling. Global inactivation of EcR increases cell death in the testis that is rescued by expression of EcR-B2 in the CySC lineage, indicating that ecdysone signaling supports stem cell viability primarily through a specific receptor isoform. Finally, EcR genetically interacts with the NURF chromatin-remodeling complex, which we previously showed maintains CySCs. Thus, although 20E levels are lower in males than females, ecdysone signaling acts through distinct cell types and effectors to ensure both ovarian and testis stem cell maintenance.
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U2 - 10.1016/j.ydbio.2014.07.016
DO - 10.1016/j.ydbio.2014.07.016
M3 - Article
C2 - 25093968
AN - SCOPUS:84910127421
SN - 0012-1606
VL - 394
SP - 129
EP - 141
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -