The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche - PubMed (original) (raw)

The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche

Liwei Wang et al. J Cell Biol. 2008.

Abstract

The stem cell niche, formed by surrounding stromal cells, provides extrinsic signals that maintain stem cell self-renewal. However, it remains unclear how these extrinsic signals are regulated. In the Drosophila female germline stem cell (GSC) niche, Decapentaplegic (DPP) is an important niche factor for GSC self-renewal. The exact source of the DPP and how its transcription is regulated in this niche remain unclear. We show that dpp is expressed in somatic cells of the niche including the cap cells, a subtype of niche cells. Furthermore, our data show that the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway positively regulates dpp expression in the cap cells, suggesting that JAK/STAT activity is required in somatic niche cells to prevent precocious GSC differentiation. Our data suggest that the JAK/STAT pathway functions downstream/independently of cap cell formation induced by Notch signaling. JAK/STAT signaling may also regulate dpp expression in the male GSC niche, suggesting a common origin of female and male GSC niches.

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Figures

Figure 1.

Figure 1.

Ectopic JAK/STAT signaling induces the formation of ectopic GSC-like cells. (A) A cartoon represents GSCs and the niche. The niche is comprised of TFs, cap cells (CpCs), and ESCs. GSCs and CBs contain a specrtosome (spherical structure in red), and differentiating cysts contain a fusome (branched structure in red), (B) a wild-type germarium, (C and D) upd overexpressing germaria, and (E) a flp-out germarium contained extra spectrosome-containing cells; (F) a stat92eTS germarium did not contain GSC, (G) stat92eTS suppressed the formation of ectopic spectrosome-containing cells in upd overexpressing germarium, (H) bam:GFP is turn off in wild-type GSC, (I) spectrosome-containing cells in upd overexpressiong germarium did not express bam:GFP. Anterior toward left. Bars: 10 μm (B and C, and E–I): 20 μm (D).

Figure 2.

Figure 2.

JAK/STAT signaling regulates dpp expression in the GSC niche. Most GSC-like cells in upd overexpressing germarium expressed high levels of Dad-lacZ (compare B with A) and pMad (compare D with C). (E) A dpp+/− germarium, (F) extra GSC-like cell phenotype in upd overexpressing germaria was suppressed by removing one copy of dpp. Ectopic dpp expression in wild type (G) and stat92eTS (H) resulted in the formation of ectopic GSC-like cells. (I) JAK/STAT signaling activity could be detected in cap cells using a STAT-GFP reporter. (J) GSCs in stat92eTS showed low pMad expression. (K) dpp transcripts were detected in cap cells marked by lamC, the punctuated signal likely reflects the dpp RNA in RNP granule or the nascent transcripts (L) sense probe as control, (L′) phase-contrast image, (M) dpp transcripts were strongly reduced in stat92eTS germarium but up-regulated in upd overexpressing germarium (N), (O) compromising Stat92e activity in cap cells resulted in GSC loss, mutant clones lack GFP signal and were marked by white-dot circle. Anterior toward left. Bars: 10 μm (B–F, I–O); 20 μm (G and H).

Figure 3.

Figure 3.

JAK/STAT signaling functions downstream or in parallel of N pathway. Similar number of lamin C–positive cap cells were present in (A) wild-type, (B) c587-GAL4; uas-upd, and (C) stat92eTS germaria. Note that there are more lamin C–positive cap cells when N signaling was ectopically activated in wild-type (D), dpp+/− (E), and stat92eTS (F) background. Anterior toward left. Bars, 10 μm.

Figure 4.

Figure 4.

JAK/STAT signaling may regulate dpp expression in male testis. (A–C) phase-contrast images of adult (A) wild-type, (B) stat92eTS (2 d after temperature shift in 31°C), and (C) c587-GAL4; uas-upd testes. Note there is drastic enlargement of anterior tip. pMad expression was down-regulated in stat92eTS (compare E with D) but up-regulated in upd overexpressing germarium (compare F with D). Hub cells are outlined with white dots in D and E. dpp expression was not detected in wild-type testis (G) by RNA in situ, but was highly expressed in upd overexpressing testis (H, arrows). Anterior toward left (except in H) and marked by asterisk. Bars: 200 μm (A–C and G–H); 20 μm (D–F).

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