Wnt glycoproteins signal through Frizzled receptors to regulate many aspects of neural development such as neuronal migration and polarity1,2,3,4. The two Frizzled receptors LIN-17 and MIG-1 appear to play antagonistic roles in certain developmental contexts3,5. In worms mutant for the Frizzled receptor LIN-17, the polarity of the PLM mechanosensory neuron is reversed. Mutations in
lin-44, which encodes one of the Wnt proteins, caused similar PLM phenotypes. Synapses made by the anterior process in wild-type animals are now made by the posterior process of mutant PLMs1,2. A similar phenotype is seen when another Frizzled, MIG-1, is over expressed in the PLM suggesting an antagonistic relationship between
lin-17 and
mig-1. Consistent with this hypothesis, loss of MIG-1 suppresses the polarity reversal of
lin-17 and
lin-44 mutants. We propose two explanations for how excess MIG-1 may cause a reversal of PLM polarity. In model 1, increased MIG-1 signaling antagonizes LIN-17 signaling. In model 2, excess MIG-1 competes with LIN-17 for the Wnt ligand LIN-44, thereby reducing signaling through LIN-17, and possibly another Wnt receptor. Model 1 predicts that loss of the MIG-1 Wnt ligand should suppress the PLM polarity defect caused by excess MIG-1. Loss of
cwn-1,
cwn-2 or
mom-2 does not ameliorate the polarity phenotype. This lack of a genetic interaction suggests that MIG-1 might bind LIN-44 to prevent it from interacting with LIN-17, inconsistent with a MIG-1 signaling role proposed in model 1. We are attempting to distinguish between these two models by determining which domains of MIG-1 are necessary and sufficient to generate the PLM polarity defect. 1. Prasad BC, Clark SG. (2006) Development 133: 1757-1766 2. Hilliard MA, Bargmann CI. (2006) Developmental Cell 10: 379-390 3. Pan C-L, et al. (2006) Developmental Cell 10: 367-377 4. Maloof JN, Whangbo J, et al. (1999) Development 126: 37-49 5. Forrester, W.C., Kim, C., Garriga, G. (2004) Genetics 168: 1951-1962.