gone early, a Novel Germline Factor, Ensures the Proper Size of the Stem Cell Precursor Pool in the Drosophila Ovary

Abstract

In order to sustain lifelong production of gametes, many animals have evolved a stem cell–based gametogenic program. In the Drosophila ovary, germline stem cells (GSCs) arise from a pool of primordial germ cells (PGCs) that remain undifferentiated even after gametogenesis has initiated. The decision of PGCs to differentiate or remain undifferentiated is regulated by somatic stromal cells: specifically, epidermal growth factor receptor (EGFR) signaling activated in the stromal cells determines the fraction of germ cells that remain undifferentiated by shaping a Decapentaplegic (Dpp) gradient that represses PGC differentiation. However, little is known about the contribution of germ cells to this process. Here we show that a novel germline factor, Gone early (Goe), limits the fraction of PGCs that initiate gametogenesis. goe encodes a non-peptidase homologue of the Neprilysin family metalloendopeptidases. At the onset of gametogenesis, Goe was localized on the germ cell membrane in the ovary, suggesting that it functions in a peptidase-independent manner in cell–cell communication at the cell surface. Overexpression of Goe in the germline decreased the number of PGCs that enter the gametogenic pathway, thereby increasing the proportion of undifferentiated PGCs. Inversely, depletion of Goe increased the number of PGCs initiating differentiation. Excess PGC differentiation in the goe mutant was augmented by halving the dose of argos, a somatically expressed inhibitor of EGFR signaling. This increase in PGC differentiation resulted in a massive decrease in the number of undifferentiated PGCs, and ultimately led to insufficient formation of GSCs. Thus, acting cooperatively with a somatic regulator of EGFR signaling, the germline factor goe plays a critical role in securing the proper size of the GSC precursor pool. Because goe can suppress EGFR signaling activity and is expressed in EGF-producing cells in various tissues, goe may function by attenuating EGFR signaling, and thereby affecting the stromal environment.

Smad-Independent BMP Signaling in Somatic Cells Limits the Size of the Germline Stem Cell Pool

“…Although we do not know how Tkv affects hh transcription, our genetic data suggest that Tkv acts upstream of Egfr, since overexpressing a constitutively active form of Egfr suppressed tkvKD -induced SCC accumulation. However, our RNA-seq results revealed that transcript levels of egfr and genes encoding Egfr ligand (Spitz) ( Tio et al., 1994 ) and modulators (Argos and Gone early) ( Klein et al., 2004 , Matsuoka et al., 2014 ) were not affected in somatic tkvKD ovaries. We speculate that non-canonical Dpp signaling may control Egfr at a post-transcriptional level, or it may influence the competence of ICs to respond to the Spitz signal.…”

Single-cell expression profile of Drosophila ovarian follicle stem cells illuminates spatial differentiation in the germarium

“…7 F). However, the same pattern is seen for gone early ( goe) which can attenuate EGFR signaling [ 64 ], and a gene often induced by EGFR pathway activity, kekkon1 ( kek1 ) [ 65 ], does not decline from ECs to FSCs. Two fibroblast growth factor (FGF) ligands, pyramus ( pyr ) and thisbe ( ths ), decline from group 5 to group 1, while the FGF antagonist sprouty ( sty ) undergoes the converse change.…”

Inactive metallopeptidase homologs: the secret lives of pseudopeptidases

“…Gone early (Goe) is an inactive pseudopeptidase member of the M13 neprilysin family in Drosophila ( Matsuoka et al, 2014 ), with substitutions in all key active site positions ( Table 2 ). Goe is a type II transmembrane protein that was detected on germ cell membranes that interfaced with other germ cells, but not on neighboring somatic cells.…”