Caenorhabditis elegans VEM-1, a novel membrane protein, regulates the guidance of ventral nerve cord-associated axons.
In the developing CNS, pathfinding growth cones use intermediate target- and pioneer axon-associated guidance cues to navigate along stereotypical trajectories. We previously showed that the novel membrane-associated protein Vema is localized to the floor plate and the optic chiasm, intermediate targets located at the ventral midline of the spinal cord and diencephalon in the developing rodent CNS, respectively. Here, we report that the Caenorhabditis elegans ortholog of vema, vem-1, is expressed by the AVG pioneer midline neuron and by several neurons that extend longitudinally projecting axons into the ventral nerve cord (VNC). In vem-1 mutants and vem-1 (RNAi) animals, a subset of posteriorly projecting interneuron axons either fail to extend ventrally to the VNC and, instead, assume aberrant lateral positions or are inappropriately located in the left tract of the VNC. In addition, ventral motor neuron axons exhibit pathfinding errors within the VNC and along the dorsoventral body axis. The conserved UNC-40/DCC and SAX-3-/Robo receptors mediate signaling events that regulate axon guidance in a wide variety of systems. Double-mutant analyses reveal that vem-1 genetically interacts with unc-40 and is likely to function in parallel with sax-3 to regulate the guidance of a subset of VNC-associated interneuron and motor neuron axons. Consistent with these genetic data, we also show that VEM-1 is capable of physically interacting with UNC-40 but not SAX-3.
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Erik
E
Runko
Zaven
Z
Kaprielian
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D017930:Genes, Reporter; D007395:Interneurons / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000097905:Roundabout Proteins
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C102174:UNC-40 protein, C elegans; C494779:VEM-1 protein, C elegans; C403927:VEMA antigen