Dumbbell anterolateral spinocranial neurofibroma with a note on thigh muscle atrophy and fasciculation.
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The gene unc-76 (unc, uncoordinated) is necessary for normal axonal bundling and elongation within axon bundles in the nematode Caenorhabditis elegans. The UNC-76 protein and two human homologs identified as expressed sequence tags are not similar to previously characterized proteins and thus represent a new protein family. At least one of these human homologs can function in C. elegans, suggesting that it, like UNC-76, acts in axonal outgrowth. We propose that the UNC-76 protein, which is found in cell bodies and processes of all neurons throughout development, either has a structural role in the formation and maintenance of axonal bundles or transduces signals to the intracellular machinery that regulates axonal extension and adhesion.
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Neurotactin (NRT), a member of the cholinesterase-homologous protein family, is a heterophilic cell adhesion molecule that is required for proper axon guidance during Drosophila development. In this study, we identify amalgam (AMA), a member of the immunoglobulin superfamily, as a ligand for the NRT receptor. Using transfected Schneider 2 cells and embryonic primary cultures, we demonstrate that AMA is a secreted protein. Furthermore, AMA is necessary for NRT-expressing cells both to aggregate with themselves and to associate with embryonic primary culture cells. Aggregation assays performed with truncated NRT molecules reveal that the integrity of the cholinesterase-like extracellular domain was not required either for AMA binding or for adhesion, with only amino acids 347-482 of the extracellular domain being necessary for both activities. Moreover, the NRT cytoplasmic domain is required for NRT-mediated adhesion, although not for AMA binding. Using an ama-deficient stock, we find that ama function is not essential for viability. Pupae deficient for ama do exhibit defasciculation defects of the ocellar nerves similar to those found in nrt mutants.
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