David Miller
Last active: 3/26/2019

UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit.

Schneider J, Skelton RL, Von Stetina SE, Middelkoop TC, van Oudenaarden A, Korswagen HC, Miller DM
Development. 2012 139 (12): 2234-45

PMID: 22619391 · PMCID: PMC3357913 · DOI:10.1242/dev.075184

Coordinated movement depends on the creation of synapses between specific neurons in the motor circuit. In C. elegans, this important decision is regulated by the UNC-4 homeodomain protein. unc-4 mutants are unable to execute backward locomotion because VA motor neurons are mis-wired with inputs normally reserved for their VB sisters. We have proposed that UNC-4 functions in VAs to block expression of VB genes. This model is substantiated by the finding that ectopic expression of the VB gene ceh-12 (encoding a homolog of the homeodomain protein HB9) in unc-4 mutants results in the mis-wiring of posterior VA motor neurons with VB-like connections. Here, we show that VA expression of CEH-12 depends on a nearby source of the Wnt protein EGL-20. Our results indicate that UNC-4 prevents VAs from responding to a local EGL-20 cue by disabling a canonical Wnt signaling cascade involving the Frizzled receptors MIG-1 and MOM-5. CEH-12 expression in VA motor neurons is also opposed by a separate pathway that includes the Wnt ligand LIN-44. This work has revealed a transcriptional mechanism for modulating the sensitivity of specific neurons to diffusible Wnt ligands and thereby defines distinct patterns of synaptic connectivity. The existence of comparable Wnt gradients in the vertebrate spinal cord could reflect similar roles for Wnt signaling in vertebrate motor circuit assembly.

MeSH Terms (20)

Animals Biomarkers Caenorhabditis elegans Caenorhabditis elegans Proteins Gap Junctions Genes, Helminth Glycoproteins Green Fluorescent Proteins Homeodomain Proteins Interneurons Models, Anatomic Motor Neurons Movement Nerve Net Nuclear Proteins Receptors, Wnt Recombinant Fusion Proteins Synapses Transcription Factors Wnt Signaling Pathway

Connections (3)

This publication is referenced by other Labnodes entities:

Links