Somatic CG6015 mediates cyst stem cell maintenance and germline stem cell differentiation via EGFR signaling in Drosophila testes

Qianwen Zheng,Jie Fang,Yidan Yan,Bo Zheng,Wanyin Chen,Yibo Wu,Min Wang,Xing Hu,Xiaojin Luan,Xia Chen,Chen Qiao,Cong Shen,Jun Yu

doi:10.1038/s41420-021-00452-w

Abstract

Stem cell niche is regulated by intrinsic and extrinsic factors. In the Drosophila testis, cyst stem cells (CySCs) support the differentiation of germline stem cells (GSCs). However, the underlying mechanisms remain unclear. In this study, we found that somatic CG6015 is required for CySC maintenance and GSC differentiation in a Drosophila model. Knockdown of CG6015 in CySCs caused aberrant activation of dpERK in undifferentiated germ cells in the Drosophila testis, and disruption of key downstream targets of EGFR signaling (Dsor1 and rl) in CySCs results in a phenotype resembling that of CG6015 knockdown. CG6015, Dsor1, and rl are essential for the survival of Drosophila cell line Schneider 2 (S2) cells. Our data showed that somatic CG6015 regulates CySC maintenance and GSC differentiation via EGFR signaling, and inhibits aberrant activation of germline dpERK signals. These findings indicate regulatory mechanisms of stem cell niche homeostasis in the Drosophila testis.

Highlights

Stem cell homeostasis is regulated by its microenvironments or stem cell niches[1]
Somatic CG6015 is required for cyst stem cells (CySCs) maintenance and germline stem cells (GSCs) differentiation
The number of pointed fusomes in tj > CG6015 RNA interference (RNAi) testes was significantly higher than that in controls (Fig. 1g). These results suggested that CG6015 regulates CySC characteristics, and nonautonomously affects germ cell differentiation

Summary

Introduction

Stem cell homeostasis is regulated by its microenvironments or stem cell niches[1]. In Drosophila, the testes contain a well-structured microenvironment comprising terminally differentiated somatic cells (hub cells), germline stem cells (GSCs), and somatic cyst stem cells (CySCs), which provides functional signals for the homeostasis of self-renewal and differentiation[2]. GSCs and CySCs divide asymmetrically to produce two kinds of daughter cells: one remains in contact with the hub and retains self-renewal characteristics, while the other is displaced from the hub and undergoes initial differentiation[4,5,6]. Somatic activation of the Hedgehog (Hh) signaling pathway in CySCs regulates the maintenance of CySC characteristics and GSC fate determination[13].

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