We aimed to isolate new recessive alleles for genes implicated in homeostatic regulation of germline stem cell (GSC) proliferation using an indirect tumorous readout. We used a non-conditional
fog-1 loss-of-function mutation to prevent sperm formation and induce unfertilized oocyte accumulation, to promote GSC quiescence through a homeostatic response mechanism. We combined
fog-1 to the thermosensitive
glp-1(
ar202) gain-of-function allele, which prevents GSC differentiation at the restrictive temperature and induces the formation of germline tumours (Pepper et al. 2003). When these doubles are grown at the permissive temperature until the late L4 stage, then upshifted to the restrictive temperature, they can form a number of oocytes that accumulate in the proximal gonad arms, but do not develop germline tumours due to the action of the homeostatic mechanism that signals to the GSCs (Narbonne et al. 2015). We screened in that background for animals that still formed germline tumours despite having accumulated oocytes. Amongst other mutants, we picked a loss-of-function allele in the
mig-6 gene, which we called
qz2. MIG-6 is a component of the extracellular matrix that is homologous to mammalian papilin, and has two isoforms. The short
mig-6 isoform is implicated in embryogenesis and phase two of distal tip cell (DTC) migration, while the long isoform cell-autonomously affects the rate of DTC migration (Kawano et al. 2009). The
mig-6(
qz2) mutation specifically disrupts the C-terminal PLAC domain of the long MIG-6 isoform. The rate of GSC proliferation in
fog-1;
mig-6(
qz2) animals is however normal, indicating that
mig-6(
qz2) does not prevent homeostatic regulation of GSC proliferation. Yet, on their own,
mig-6(
qz2) mutants have a slightly reduced brood size and a small percentage of embryonic lethality. The distal parts of their gonad arms are 30% shorter and 43% wider than in wild-type, while the turns and proximal arms appear normally constituted. The DTCs in
mig-6(
qz2) animals are also less elongated and wider than in wild-type, while
lag-2 expression appears unchanged.
glp-1(
ar202) mutants develop germline tumors at 25 deg C but are nearly wild type at 15 deg C. We found that
mig-6(
qz2) greatly aggravates the
glp-1(
ar202)gf phenotypes at the permissive temperature. Indeed, we observed an important decrease in brood size, a much higher embryonic and larval lethality, and the frequent formation of germline tumors in the
glp-1(
ar202)gf;
mig-6(
qz2) double mutant than in either single mutant. Our data therefore suggest that the PLAC domain of the long MIG-6 isoform acts to functionally dampen
glp-1 signalling.