Recent advances in Drosophila male germline stem cell biology

Abstract

The ability of stem cells to divide asymmetrically to produce both self-renewing and differentiating daughter cells sustains many adult tissues, but germline stem cells (GSCs) are unique among stem cells as they perpetuate the genome of the species. The cellular and molecular mechanisms regulating most mammalian stem cells in their endogenous local microenvironments, or niches, are quite challenging to study. However, studies of stem cell niches such as those found in the Drosophila gonads have proven very useful. In these tissues, GSCs are housed in a readily identifiable niche, and the ability to genetically manipulate these cells and their neighbors has uncovered several fundamental mechanisms that are relevant to stem cells more generally. Here, we summarize recent work on the regulation of GSCs in the Drosophila testis niche by intercellular signals, and on the intracellular mechanisms that cooperate with these signals to ensure the survival of the germline. This review focuses on GSCs within the adult Drosophila testis; somatic stem cells in this tissue are reviewed by Zoller and Schulz in this issue.(1) For a review of the testis niche as a whole, see de Cuevas and Matunis,(2) and for more comprehensive reviews of the Drosophila testis, refer to Fuller(3) and Davies and Fuller.(4).

Figure 1. The Drosophila testis stem cell niche. Stromal hub cells (green) adhere to the apical tip of the testis. Surrounding the hub are germline stem cells (GSCs, yellow) and somatic cyst stem cells (CySCs, blue), which share the niche. GSCs and CySCs divide and produce daughter cells that remain in the niche (self-renewal) or leave the niche and differentiate. GSCs give rise to spermatogonia (light yellow), which ultimately develop into sperm; CySCs give rise to cyst cells (light blue), which encase the developing spermatogonia. The fusome (red), a germline-specific endoplasmic reticulum-like organelle, has a spherical shape in GSCs and gonialblast daughters and an elongated or branched shape in spermatogonia. (Adapted from ref. .)

Figure 2. Local and systemic signals maintain testis stem cells. Hub cells (green) secrete the ligand Upd, which activates JAK-STAT signaling in adjacent germline stem cells (GSCs) and somatic cyst stem cells (CySCs). In CySCs (blue), JAK-STAT activation is sufficient for CySC self-renewal. GSCs (yellow) are maintained by signals from both the hub and CySCs that independently regulate GSC self-renewal and adhesion to the hub. Two BMP ligands, Dpp and Gbb (produced by hub cells and CySCs), activate BMP signaling in GSCs, leading to repression of the differentiation factor Bam. The epigenetic factors NURF, Nclb, and Phf7 are all required for maintenance of the GSCs. Insulin signaling also helps to maintain GSCs. Stg promotes proliferation in the GSCs while EGF signaling attenuates proliferation in the GSCs. In CySCs, BMP ligands might be produced in response to activated STAT or one or more of its targets, or in response to Ken. (Adapted from reference 87). Bam, Bag of marbles; BMP, Bone morphogenetic protein; Chinmo, chronologically inappropriate morphogenesis; Dpp, decapentaplegic; EGF, epidermal growth factor; Ken, ken and barbie; Lar, Leukocyte-antigen-related-like; NURF, nucleosome remodeling factor; Nclb, No child left behind; Phf7, PHD Finger Protein 7; Gbb, glass bottom boat; JAK, Janus kinase; Socs36E, Suppressor of cytokine signaling at 36E; STAT, signal transducer and activator of transcription; Stg, string; Upd, Unpaired; Zfh1, Zinc-finger homeodomain protein 1.