Figure 2: Signaling pathways in the adult Drosophila testis.
Hub cells (yellow) produce Bone morphogenetic proteins (BMPs), the JAK/STAT ligand Unpaired (Upd), and the Hedgehog (Hh) pathway ligand Hh.
GSCs (pink) transduce BMP signaling through phosphorylation of the transcription factor Mad. BMP signaling represses expression of the germline differentiation factor bam, thereby promoting GSC self-renewal (circular arrow). BMP signaling also represses expression of the transcriptional co-repressor Hairless (H). H in turn represses expression of Imp, an RNA-binding protein. Imp promotes expression of Chinmo. High levels of Chinmo repress GSC competition, while loss of Chinmo promotes GSC competition. The lipase Brummer has also be shown to repress GSC competition.
CySCs (blue) activate transcription factors STAT and Ci, effectors of the JAK/STAT and Hh pathways. Activated phospho-STAT (pSTAT) activates target genes including Socs36E, Chinmo, and Zfh1; Ci also activates Zfh1. STAT through Chinmo and Zfh1 promotes CySC self-renewal (circular arrow). Zfh1 represses expression of Hippo pathway components Salvador (Sav) and Kibra (not shown), which restricts Yorkie (Yki) activation to Zfh1-positive cells. Yki promotes CySC self-renewal. Additionally, activation of Yki induces CySC-CySC competition. Socs36E is an induced negative feedback inhibitor of the JAK/STAT pathway, and it also inhibits Egfr/Ras/MAPK signaling. Egfr signaling in CySCs is activated by the EGF ligand Spitz (Spi) from germ cells. Egfr/Ras/MAPK is required for CySC self-renewal but plays a stronger role in CySC-CySC competition. Abl represses CySC-CySC.
The relative sizes of the activating and inhibitory arrows in CySCs indicate whether the factor more strongly regulates self-renewal or intra-lineage competition.