Hedgehog is required for CySC self-renewal but does not contribute to the GSC niche in the Drosophila testis

Abstract

The Drosophila testis harbors two types of stem cells: germ line stem cells (GSCs) and cyst stem cells (CySCs). Both stem cell types share a physical niche called the hub, located at the apical tip of the testis. The niche produces the JAK/STAT ligand Unpaired (Upd) and BMPs to maintain CySCs and GSCs, respectively. However, GSCs also require BMPs produced by CySCs, and as such CySCs are part of the niche for GSCs. Here we describe a role for another secreted ligand, Hedgehog (Hh), produced by niche cells, in the self-renewal of CySCs. Hh signaling cell-autonomously regulates CySC number and maintenance. The Hh and JAK/STAT pathways act independently and non-redundantly in CySC self-renewal. Finally, Hh signaling does not contribute to the niche function of CySCs, as Hh-sustained CySCs are unable to maintain GSCs in the absence of Stat92E. Therefore, the extended niche function of CySCs is solely attributable to JAK/STAT pathway function.

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

“…We monitored the activities of these pathways in CySCs upon lwr or Su(var)2-10 suppression driven by c587-Gal4. Patched (Ptc) expression has been used as readout of the Hh pathway (Amoyel et al, 2013;Michel et al, 2012). We found that the level of Ptc was reduced in lwr RNAi testes compared with control ( Fig.…”

“…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.…”

Traffic jam functions in a branched pathway from Notch activation to niche cell fate

“…Hedgehog secreted from the hub activates signaling within the CySC lineage. This is visualized by punctate accumulation of the receptor Patched (Ptc), representing trafficking intermediates (Amoyel et al, 2013;Michel et al, 2012). In late L1 controls, Ptc is enriched around the hub (Fig.…”

“…The hub cells secrete bone morphogenetic proteins (BMPs) and the cytokine Unpaired to activate self-renewal and adhesion in the GSCs (Kawase et al, 2004;Kiger et al, 2001;Leatherman and DiNardo, 2010;Shivdasani and Ingham, 2003;Tulina and Matunis, 2001). An additional component of the niche, the cyst stem cell (CySC) lineage, is maintained by Unpaired and Hedgehog secreted from the hub DiNardo, 2008, 2010;Amoyel et al, 2013;Michel et al, 2012). Steady-state function of the niche is established within the larval gonad following hub cell specification and stem cell recruitment (Le Bras and Van Doren, 2006;Sheng et al, 2009;Sinden et al, 2012).…”

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

“…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).…”