"The U-shape of the gonad arms is formed by directional movement of distal tip cells (DTCs), which is regulated by MIG-17, an ADAMTS protease. To obtain further insights into the molecular mechanisms of DTC migration involving MIG-17, we isolated suppressor mutants of
mig-17 DTC migration defects. One of these,
k185 was a dominant suppressor and we identified a missense mutation in the
mig-22 gene on LGIII. We previously reported that the MIG-22 protein is chondroitin polymerizing factor, a co-factor for chondroitin synthase whose loss-of-function mutations
(k141 and
tk24) cause abnormal DTC migration similar to that seen in
mig-17 mutants (Suzuki et al., Dev. Biol. 300: 635, 2006). Double mutants between
mig-17(null) and
mig-22 alleles showed enhanced DTC migration defects, suggesting that these genes do not constitute a single pathway. Because
mig-22(
k185) mutant showed normal DTC migration,
k185 does not appear to be a simple loss-of-function mutation. The suppression activity was strongest in
k185/185, moderate in
k185/+, weak in
k185/0 and no activity in +/+, indicating that
k185, is a gain-of-function mutation. A mutation in
mig-22(
k185) does not affect the amount of chondroitin or the levels of MIG-22 proteins. The expression of the
mig-22(
k185) gene under the control of the
mig-24 promoter, which drives gene expressed in DTCs, rescued DTC migration defects of
mig-17 mutants. Transgenic expression of the wild-type
mig-22 under either a DTC or a seam cell-specific promoter also rescued
mig-17. The expression of
sqv-5, a gene for chondroitin synthase, under the
mig-22 promoter failed to rescue
mig-17. Surprisingly, however, abnormal DTC migration in
sqv-5 (null) was rescued by
mig-22(
k185). In
sqv-5(null);
mig-17(null) animals,
mig-22(
k185) could not rescue the abnormal DTC migration, suggesting that the rescuing activity of
mig-22(
k185) for
mig-17(null) depends on the function of SQV-5. We are examining whether specific chondroitin proteoglycans are involved in
mig-22(
k185) dependent-suppression of
mig-17 by RNAi knockdown of core protein genes
cpg1-9 reported by Olson et al., JCB 173: 985, 2006."