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Comments on Skelton, Rachel L et al. (2009) International Worm Meeting "unc-4 antagonizes a Wnt signaling pathway upstream of ceh-12/HB9 to specify synaptic choice in the C. elegans motor circuit." (0)
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Skelton, Rachel L, Schneider, Judsen, Von Stetina, Stephen, Watkins, Kathie, & Miller III, David M (2009). unc-4 antagonizes a Wnt signaling pathway upstream of ceh-12/HB9 to specify synaptic choice in the C. elegans motor circuit presented in International Worm Meeting. Unpublished information; cite only with author permission.
Neural function depends on the creation of synapses between specific neurons. In C. elegans, this important developmental decision is regulated by the UNC-4 homeodomain protein. UNC-4 functions in VA motor neurons to block the adoption of inputs normally reserved for VB sister cells. This wiring defect in unc-4 mutants disables backward locomotion. Thus, we have proposed that UNC-4 preserves normal VA inputs and backward movement by inhibiting VB gene expression. This model was substantiated by our previous finding that ectopic expression of the VB-specific gene, ceh-12 (HB9 homeodomain protein), results in the miswiring of VA motor neurons in the posterior ventral nerve cord. Now we have used cell-specific microarray profiling and independent mutant screens to establish that ectopic expression of CEH-12/HB9 in posterior VA motor neurons depends on a response to a local source of EGL-20/Wnt. Our results show that unc-4 antagonizes a Wnt signaling pathway involving egl-20/Wnt, mom-5/Frz, and mig-1/Frz that is required for ceh-12 expression in VA motor neurons. We propose that UNC-4 represses mom-5/Frz expression, thereby rendering VA motor neurons unresponsive to EGL-20/Wnt. RNAi and genetic experiments have revealed additional Wnt signaling components that interact with the unc-4 pathway, including the Frizzled receptor, lin-17, lin-44/Wnt, dsh-1/Disheveled, pry-1/Axin, and pop-1/TCF-LEF. Further investigation will determine if these canonical Wnt pathway components function upstream of ceh-12 or in a parallel pathway. This work has revealed a sensitive mechanism for exploiting diffusible Wnt ligands for precise patterning of connectivity in the C. elegans ventral nerve cord. The existence of comparable Wnt gradients in the vertebrate spinal cord could reflect similar but as yet unexplored roles for Wnt signaling in vertebrate motor circuit assembly.