Upregulated TNF/Eiger signaling mediates stem cell recovery and tissue homeostasis during nutrient resupply in Drosophila testis

Yi Chieh Chang,Hsin Tu,To-Wei Huang,Bo-Wen Xu,Haiwei Pi

doi:10.1038/s41598-020-68313-7

Yi Chieh Chang, Hsin Tu + Show 3 more

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https://doi.org/10.1038/s41598-020-68313-7

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Abstract

Stem cell activity and cell differentiation is robustly influenced by the nutrient availability in the gonads. The signal that connects nutrient availability to gonadal stem cell activity remains largely unknown. In this study, we show that tumor necrosis factor Eiger (Egr) is upregulated in testicular smooth muscles as a response to prolonged protein starvation in Drosophila testis. While Egr is not essential for starvation-induced changes in germline and somatic stem cell numbers, Egr and its receptor Grindelwald influence the recovery dynamics of somatic cyst stem cells (CySCs) upon protein refeeding. Moreover, Egr is also involved in the refeeding-induced, ectopic expression of the CySC self-renewal protein and the accumulation of early germ cells. Egr primarily acts through the Jun N-terminal kinase (JNK) signaling in Drosophila. We show that inhibition of JNK signaling in cyst cells suppresses the refeeding-induced abnormality in both somatic and germ cells. In conclusion, our study reveals both beneficial and detrimental effects of Egr upregulation in the recovery of stem cells and spermatogenesis from prolonged protein starvation.

Highlights

Stem cell activity and cell differentiation is robustly influenced by the nutrient availability in the gonads
Since Jun N-terminal kinase (JNK) signaling is activated in cyst cells in response to amino acid starvation[3], we asked if protein starvation induces Egr protein upregulation in testicular smooth muscles
By examining the levels of Egr-GFP expressed from a genomic fosmid clone[23], upregulation of GFP in smooth muscles was observed in testes from flies suffered from prolonged protein starvation (Fig. 1B– D)

Summary

Introduction

Stem cell activity and cell differentiation is robustly influenced by the nutrient availability in the gonads. We show that tumor necrosis factor Eiger (Egr) is upregulated in testicular smooth muscles as a response to prolonged protein starvation in Drosophila testis. While Egr is not essential for starvation-induced changes in germline and somatic stem cell numbers, Egr and its receptor Grindelwald influence the recovery dynamics of somatic cyst stem cells (CySCs) upon protein refeeding. In female Drosophila, egg production is dramatically reduced under the protein-poor d iet[2] This is partly due to the reduced division rate of both GSCs and follicle stem cells, and their progeny. Starvation-induced spermatogonia death is triggered by the apoptosis of the surrounding somatic cyst c ells[3], which enclose the germ cells to regulate their self-renewal, proliferation and differentiation[4,5,6,7,8].

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