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Background: Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) form one of the largest and most diverse families of adhesion molecules and receptors in the nervous system. Many members of this family mediate contact and communication among neurons during development. The Caenorhabditis elegans genome contains a comparatively small number of IgCAMs, most of which are evolutionarily conserved and found across all animal phyla. Only some of these have been functionally characterized so far. Results: We systematically analyzed previously uncharacterized IgCAMs in C. elegans. Green fluorescent protein reporter constructs of 12 IgCAMs revealed that expression generally is not confined to a single tissue and that all tissues express at least one of the IgCAMs. Most IgCAMs were expressed in neurons. Within the nervous system significant overlap in expression was found in central components of the motor circuit, in particular the command interneurons, ventral cord motoneurons as well as motoneurons innervating head muscles. Sensory neurons are underrepresented among the cells expressing these IgCAMs. We isolated mutations for eight of the genes showing neuronal expression. Phenotypic analysis of single mutants revealed limited neuronal defects, in particular axon navigation defects in some of the mutants. Systematic genetic interaction studies uncovered two cases of functional overlap among three and four genes, respectively. A strain combining mutations in all eight genes is viable and shows no additional defects in the neurons that were analyzed, suggesting that genetic interactions among those genes are limited. Conclusion: Genetic interactions involving multiple IgCAMs affecting axon outgrowth demonstrate functional overlap among IgCAMs during nervous system development. [ABSTRACT FROM AUTHOR]

Abstract: Neurons send out axons and dendrites over large distances into target areas where they eventually form synapses with selected target cells. Axonal navigation is controlled by a variety of extracellular signals and neurons express receptors only for that subset of signals they need to navigate to their own target area. How the expression of axon guidance receptors is regulated is not understood. In genetic screens for mutants with axon guidance defects, we identified an ETS-domain transcription factor, AST-1, specifically required for axon navigation in certain classes of interneurons. In addition, ast-1 has a role in the differentiation of the ventral cord pioneer neuron AVG. Outside the nervous system, ast-1 is essential for morphogenesis of the pharynx. Ast-1 is transiently expressed in several classes of neurons (including AVG) during neuronal differentiation with a peak expression during late stages of neuronal differentiation and axon outgrowth. Ast-1 genetically interacts with other transcription factors controlling neuronal differentiation like lin-11 and zag-1 as well as components of the netrin pathway suggesting that ast-1 might control the expression of components of the netrin signal transduction machinery. [Copyright &y& Elsevier]

Presents a study which identified a novel zinc-finger/homeodomain containing transcription factor called zag-1 required for pathway selection in Caenorhabditis elegans. Materials and methods used; Result of molecular cloning of zag-1 gene; Expression of zag-1; Role of zag-1 in neuronal differentiation.

The L1 cell adhesion molecule (L1CAM) participates in neuronal development. Mutations in the human L1 gene can cause the neurological disorder CRASH (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus). This study presents genetic data that shows that L1-like adhesion gene 2 (LAD-2), a Caenorhabditis elegans L1CAM, functions in axon pathfinding. In the SDQL neuron, LAD-2 mediates dorsal axon guidance via the secreted MAB-20/Sema2 and PLX-2 plexin receptor, the functions of which have largely been characterized in epidermal morphogenesis. We use targeted misexpression experiments to provide in vivo evidence that MAB-20/Sema2 acts as a repellent to SDQL. Coimmunoprecipitation assays reveal that MAB-20 weakly interacts with PLX-2; this interaction is increased in the presence of LAD-2, which can interact independently with MAB-20 and PLX-2. These results suggest that LAD-2 functions as a MAB-20 coreceptor to secure MAB-20 coupling to PLX-2. In vertebrates, L1 binds neuropilin 1, the obligate receptor to the secreted Sema3A. However, invertebrates lack neuropilins. LAD-2 may thus function in the semaphorin complex by combining the roles of neuropilins and L1CAMs. [ABSTRACT FROM AUTHOR]