Direct control of somatic stem cell proliferation by theDrosophilatestis stem cell niche

Abstract

Niches are traditionally characterized as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes the integration of multiple niche signals towards a binary decision between stemness and differentiation. However, observations in multiple systems have demonstrated that stem cell properties such as proliferation and differentiation can be uncoupled at the level of niche signalling input, which is incompatible with this traditional view. We have studied the role of the transcriptional regulator Zfh1, a shared target of the Hedgehog and Jak/Stat niche signalling pathways in the somatic cyst stem cells of the Drosophila testis. We demonstrate that Zfh1 binds and downregulates salvador and kibra, two tumour suppressor genes of the Hippo/Wts/Yki pathway. Yki activation is thereby restricted to the Zfh1 positive stem cells, which are hence the only somatic cell able to proliferate. Our observations therefore trace a direct connection from stem cell proliferation back to niche signal input, and provide a mechanistic example for the "micromanagement" of an individual aspect of stem cell behaviour by the niche.Niche control of stem cell proliferation

Identification and Functional Characterization of Muscle Satellite Cells in Drosophila

“…Thus in adult muscle, cells labeled by a Zfh1 antibody are clearly unfused and located closely apposed to the mature muscle fibers (Figure 4B-D). Similar highly specific labeling of unfused muscle satellite cells is observed in adult muscle with either a GFP-tagged Zfh1 protein or with a Zfh1-fused Gal4 driver and a UASRedStinger reporter ( Figure 4E, F) (30). In all cases Zfh1 expression is limited to unfused cells and is never seen inside intact adult muscle fibers.…”

“…F1-Progenies, N> GTRACE, from this cross were used for the experimental analysis. The following strains were a kind gift from Christian Böekel (Technische Universität Dresden) : +;+;Zfh1-T2A-Gal4, tub-Gal80 ts /TM3 , +;+;Zfh1::GFP/TM3 (30). Crosses were set with +;+;Zfh1-T2A-Gal4, tub-Gal80 ts /TM3 and GTRACE/Cyo; Gal80 ts (Lolitika Mandal, IISCER, Mohali) animals at 18 degrees C. Eclosed animals between 1 to 3 days of age were shifted to 29 degrees C for 72h before injury.…”

Innate immune signalling drives loser cell elimination during stem cell competition in theDrosophilatestis

“…For the pattB 3xRelBS-GFPnls construct we combined a tandem triplicated Rel binding site and Hsp70 minimal promoter with the GFPnls ORF taken from pSav-GFPnls (Albert et al, 2018) and the 3'UTR and polyadenylation site from a pUAST vector modified to also contain an attB cassette. Inserting the resulting construct into the attP2 landing site yielded the w;;3xRelBS-GFPnls reporter line.…”

“…We next tested whether the rescue of stem cell state by inactivation of Rel was specific to To add another condition where elimination of clones is unambiguosly due to competition we turned to an isoform specific deletion of Zfh1, zfh1 ΔRB . Both the short isoform Zfh1-RA and the longer variant Zfh1-RB that contains two extra N-terminal zinc fingers are expressed in the testis (Albert et al, 2018). However, while a deletion of Zfh1-RA is lethal, zfh1 ΔRB flies ( Fig.…”

“…The gene encoding the NF-κB transcription factor Rel was also amongst the strongest hits in a previous screen for Zfh1 binding in the somatic cyst stem cells, marking Rel as a potential target of niche activity (Albert et al, 2018). We therefore examined a potential link between immune signalling involving Rel, niche function, and the previously observed stem cell competition.…”