From a screen for cell migration mutants, we isolated a mutation in the C.elegans Frizzled gene
cfz-2. Frizzled family members are receptors for secreted Wnt proteins. Wnt signaling regulates many developmental processes including cell fate decisions, axon guidance and cell migration. A second
cfz-2 mutation was identified by the International C.elegans Gene Knockout Consortium. In
cfz-2 mutants, the migrations of several cell types are disrupted. For example, ALM neurons migrate posteriorly during embryogenesis. In
cfz-2 mutants, ALM neurons often are located along their migratory pathway indicating that they failed to migrate fully. The right Q neuroblast and its descendants (QR) migrate anteriorly during the first larval stage. In
cfz-2 mutants, QR migrations often terminate prematurely. In addition, in
cfz-2 mutants axon morphology is sometimes aberrant, suggesting that growth cone migration is disrupted, resulting in axon guidance and branching defects. Mutation of
cfz-2 also causes disorganization of head neurons.To begin to dissect CFZ-2 function, we have investigated candidate ligands. Mutations in three C.elegans Wnts,
cwn-1,
cwn-2 and
egl-20, affect some of the same cell migrations as mutations in
cfz-2, raising the possibility that they may encode CFZ-2 ligands. Consistent with this, QR cell migrations in
cwn-2;
cfz-2 double mutants resemble those of
cwn-2 single mutants, suggesting that CWN-2 might act through CFZ-2 for QR migration. By contrast, the ALM cell migration defect of
cfz-2 mutants is suppressed by mutation in
cwn-1,
cwn-2 or
egl-20, suggesting that these Wnts oppose CFZ-2 in ALM migration. Reduction or removal of zygotic
mom-5, which encodes a second Frizzled, also suppresses the ALM defect of
cfz-2 mutants, suggesting that CWN-1, CWN-2 and/or EGL-20 may function through MOM-5 to oppose CFZ-2 in ALM cell migration. Therefore, CWN-2 may act through CFZ-2 to regulate QR cell migrations whereas CWN-2 and other Wnts may antagonize CFZ-2 to regulate other migrations. Our results suggest that a complex network of multiple Wnt/Frizzled signaling pathways regulate cell migration, in at least some cases by opposing one another.