Hh signalling is essential for somatic stem cell maintenance in the<i>Drosophila</i>testis niche

Michel, Marcus; Kupinski, Adam P.; Raabe, Isabel; Bökel, Christian

doi:10.1242/dev.075242

Cited by 94 publications

(79 citation statements)

References 47 publications

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“…In addition, Smo 3 and Ptc IIW null alleles were used to inactivate and activate Hh signaling, respectively, in mosaic analysis with a repressible cell marker (MARCM). The results showed that Smo 3 mutant CySCs disappeared rapidly, while Ptc IIW mutant CySCs were found in all testes (Supplementary information, Table S1, Figures S4 and S5), which is consistent with the recent findings by others [7].…”

Section: -Positive Cells Under Different Hh Signaling Activities (Susupporting

confidence: 91%

“…Our study identified that Hh signaling activity mainly acts in CySCs and is critical for CySC maintenance in Drosophila testis, which further confirmed an independent finding published recently [7]. In addition, we revealed three novel aspects of Hh signaling in the testis ( Figure 1Y).…”

Section: -Positive Cells Under Different Hh Signaling Activities (Susupporting

confidence: 91%

“…Hh is expressed in the hub cells as revealed by hh-lacZ and Hh stainings (Supplementary information, Figure S1), which is consistent with a recent finding from Michel M et al [7]. The stainings of Ci-lacZ, Ci, ptc-lacZ and Smo largely coincide with that of Zfh-1 expression (Supplementary information, Figure S1).…”

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confidence: 90%

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Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Zhang

Jen³

et al. 2013

Cell Res

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Stem cell niche is a specialized microenvironment crucial for stem cell self-renewal. Drosophila testis contains two types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs), providing a good model for studying niche-stem cell interaction [1]. At the apex of testis tube, non-mitotic somatic cells form a tightly folded structure called the hub. About 10 GSCs, each accompanied by 2 CySCs, make direct contact with the hub cells to form a rose-like structure (Supplementary information, Figure S1A). CySCs rely on the hub cells for niche signals, while GSCs are maintained by niche signals from both the hub cells and CySCs [1].Bone morphogenetic protein (BMP) signaling is critical for GSC maintenance [2], while Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling functions in both CySCs and GSCs. STAT activation in CySCs leads to the expression of zfh-1 [3] and chinmo [4], two factors critical for CySC self-renewal. JAK-STAT signaling does not directly regulate the selfrenewal of GSCs, but governs GSC-niche adhesion [5]. Although Zfh-1 is a direct target of activated STAT, eliminating STAT activity only decreased but did not abolish Zfh-1 expression [3], suggesting that a paralleled pathway(s) may be involved in the regulation of Zfh-1 expression. In the course of immunostaining adult flies expressing a hh enhancer trap, hh-lacZ [6], we observed a strong hh-lacZ staining at the apex of testis (Supplementary information, Figure S1), which is consistent with a previous observation that hh-lacZ was expressed in the hub cells [6], suggesting a potential function of Hedgehog (Hh) signaling in the testis.We examined the expression of several core components of the Hh pathway. Hh is expressed in the hub cells as revealed by hh-lacZ and Hh stainings (Supplementary information, Figure S1), which is consistent with a recent finding from Michel M et al. [7]. The stainings of Ci-lacZ, Ci, ptc-lacZ and Smo largely coincide with that of Zfh-1 expression (Supplementary information, Figure S1). Immunostainings and real-time PCR analyses strongly suggest that Ci, Ptc and Smo are enriched in cyst cells (Supplementary information, Figure S1 and Data S1). We used different approaches to activate or inactivate Hh signaling and used Ptc expression as a readout of Hh pathway activity, as Ptc itself is a target of Hh signaling. The results strongly argue for the presence of a functional Hh pathway in Drosophila testis (Supplementary information, Figure S2).To test whether Hh signaling functions in CySCs, we quantified the number of CySCs by calculating Zfh- 1-positive cells under different Hh signaling activities (Supplementary information, Data S1). Smo RNAi, CiRNAi or the ectopic expression of Smo PKA123 (Smo dominant negative form) driven by cyst cell-specific c587-Gal4 significantly reduced CySC number, whereas the expression of Smo SD123 (Smo active form) in cyst cells significantly increased CySC number ( Figure 1A). By contrast, knockdown of Ci or Smo using RNAi driven by germlin...

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Section: -Positive Cells Under Different Hh Signaling Activities (Susupporting

confidence: 91%

Section: -Positive Cells Under Different Hh Signaling Activities (Susupporting

confidence: 91%

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Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Zhang

Jen³

et al. 2013

Cell Res

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“…1A). Several signaling pathways have been reported to regulate CySCs, including the JAK-STAT pathway (Issigonis et al, 2009;Kiger et al, 2001;Leatherman and DiNardo, 2010;Singh et al, 2010;Tulina and Matunis, 2001), the EGFR pathway (Eun et al, 2014;Kiger et al, 2000;Tran et al, 2000), the Hpo pathway (Amoyel et al, 2014) and the Hh pathway (Amoyel et al, 2013;Michel et al, 2012;Zhang et al, 2013b). Although these pathways govern stem cell behavior, the function of PTMs during this process is rarely reported.…”

Section: Introductionmentioning

confidence: 99%

SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis

Pan

Zhang

et al. 2016

Development

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SUMO (Small ubiquitin-related modifier) modification (SUMOylation) is a highly dynamic post-translational modification (PTM) that plays important roles in tissue development and disease progression. However, its function in adult stem cell maintenance is largely unknown. Here, we report the function of SUMOylation in somatic cyst stem cell (CySC) self-renewal in adult Drosophila testis. The SUMO pathway cell-autonomously regulates CySC maintenance. Reduction of SUMOylation promotes premature differentiation of CySCs and impedes the proliferation of CySCs, which leads to a reduction in the number of CySCs. Consistent with this, CySC clones carrying a mutation of the SUMO-conjugating enzyme are rapidly lost. Furthermore, inhibition of the SUMO pathway phenocopies disruption of the Hedgehog (Hh) pathway, and can block the proliferation of CySCs induced by Hh activation. Importantly, the SUMO pathway directly regulates the SUMOylation of Hh pathway transcription factor Cubitus interruptus (Ci), which is required for promoting CySC proliferation. Thus, we conclude that SUMO directly targets the Hh pathway and regulates CySC maintenance in adult Drosophila testis.

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“…The hub secretes the JAK-STAT ligand Unpaired (Upd), Hedgehog (Hh) and bone morphogenetic proteins (BMPs) to regulate stem cell maintenance and repress differentiation in both GSCs and CySCs (de Cuevas and Matunis, 2011). Hub-derived Hh is required in CySCs for self-renewal independently of JAK-STAT signalling (Amoyel et al, 2013;Michel et al, 2012). Additionally, somagermline communication mediated by the epidermal growth factor receptor (EGFR) pathway is required during and after encapsulation (Hudson et al, 2013;Sarkar et al, 2007;Schulz et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Bi-directional gap junction-mediated Soma-Germline communication is essential for spermatogenesis

et al. 2015

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Soma-germline interactions play conserved essential roles in regulating cell proliferation, differentiation, patterning and homeostasis in the gonad. In the Drosophila testis, secreted signalling molecules of the JAK-STAT, Hedgehog, BMP and EGF pathways are used to mediate soma-germline communication. Here, we demonstrate that gap junctions may also mediate direct, bi-directional signalling between the soma and germ line. When gap junctions between the soma and germ line are disrupted, germline differentiation is blocked and germline stem cells are not maintained. In the soma, gap junctions are required to regulate proliferation and differentiation. Localization and RNAi-mediated knockdown studies reveal that gap junctions in the fly testis are heterotypic channels containing Zpg (Inx4) and Inx2 on the germ line and the soma side, respectively. Overall, our results show that bi-directional gap junction-mediated signalling is essential to coordinate the soma and germ line to ensure proper spermatogenesis in Drosophila. Moreover, we show that stem cell maintenance and differentiation in the testis are directed by gap junction-derived cues.

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Hh signalling is essential for somatic stem cell maintenance in theDrosophilatestis niche

Cited by 94 publications

References 47 publications

Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis

Bi-directional gap junction-mediated Soma-Germline communication is essential for spermatogenesis

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