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      IgCAMs redundantly control axon navigation in Caenorhabditis elegans

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          Abstract

          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.

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          Most cited references50

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          Molecular mechanisms of axon guidance.

          Axons are guided along specific pathways by attractive and repulsive cues in the extracellular environment. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules, including netrins, Slits, semaphorins, and ephrins. Guidance cues steer axons by regulating cytoskeletal dynamics in the growth cone through signaling pathways that are still only poorly understood. Elaborate regulatory mechanisms ensure that a given cue elicits the right response from the right axons at the right time but is otherwise ignored. With such regulatory mechanisms in place, a relatively small number of guidance factors can be used to generate intricate patterns of neuronal wiring.
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            PCR fusion-based approach to create reporter gene constructs for expression analysis in transgenic C. elegans.

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              Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.

              The DCC (Deleted in colorectal cancer) gene was first identified as a candidate for a tumour-suppressor gene on human chromosome 18q. More recently, in vitro studies in rodents have provided evidence that DCC might function as a receptor for the axonal chemoattractant netrin-1. Inactivation of the murine Dcc gene caused defects in axonal projections that are similar to those observed in netrin-1-deficient mice but did not affect growth, differentiation, morphogenesis or tumorigenesis in mouse intestine. These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1.
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                Author and article information

                Journal
                Neural Dev
                Neural Development
                BioMed Central
                1749-8104
                2009
                2 April 2009
                : 4
                : 13
                Affiliations
                [1 ]Max Planck Institute for Medical Research, Jahnstr., 69120 Heidelberg, Germany
                [2 ]Simon Fraser University, University Drive, Burnaby, BC, V5A 1S6, Canada
                Article
                1749-8104-4-13
                10.1186/1749-8104-4-13
                2672934
                19341471
                dc0ac8a2-e514-41bb-9ebf-945c4c617e74
                Copyright © 2009 Schwarz et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 November 2008
                : 2 April 2009
                Categories
                Research Article

                Neurosciences
                Neurosciences

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