Heparan sulfate proteoglycan specificity during axon pathway formation in the Drosophila embryo

Authors

  • Ashley D. Smart,

    1. Department of Biology and Program in Neuroscience, Pomona College, Claremont, California 91711
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  • Meredith M. Course,

    1. Department of Biology and Program in Neuroscience, Pomona College, Claremont, California 91711
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  • Joel Rawson,

    1. Department of Pediatrics and Department of Genetics, Cell Biology and Developmental Biology Center, University of Minnesota, 321 Church St. SE, Minneapolis, Minnesota 55455
    Current affiliation:
    1. Department of Physiology, University of Texas - Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78229
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  • Scott Selleck,

    1. Department of Pediatrics and Department of Genetics, Cell Biology and Developmental Biology Center, University of Minnesota, 321 Church St. SE, Minneapolis, Minnesota 55455
    Current affiliation:
    1. Department of Biochemistry and Molecular Biology, 205A Life Sciences Building, University Park, Pennsylvania 16802
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  • David Van Vactor,

    1. Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115
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  • Karl G. Johnson

    Corresponding author
    1. Department of Biology and Program in Neuroscience, Pomona College, Claremont, California 91711
    • Department of Biology and Program in Neuroscience, Pomona College, Claremont, California 91711
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Abstract

Axon guidance is influenced by the presence of heparan sulfate (HS) proteoglycans (HSPGs) on the surface of axons and growth cones (Hu, [2001]: Nat Neurosci 4:695–701; Irie et al. [2002]: Development 129:61–70; Inatani et al. [2003]: Science 302:1044–1046; Johnson et al. [2004]: Curr Biol 14:499–504; Steigemann et al. [2004]: Curr Biol 14:225–230). Multiple HSPGs, including Syndecans, Glypicans and Perlecans, carry the same carbohydrate polymer backbones, raising the question of how these molecules display functional specificity during nervous system development. Here we use the Drosophila central nervous system (CNS) as a model to compare the impact of eliminating Syndecan (Sdc) and/or the Glypican Dally-like (Dlp). We show that Dlp and Sdc share a role in promoting accurate patterns of axon fasciculation in the lateral longitudinal neuropil; however, unlike mutations in sdc, which disrupt the ability of the secreted repellent Slit to prevent inappropriate passage of axons across the midline, mutations in dlp show neither midline defects nor genetic interactions with Slit and its Roundabout (Robo) receptors at the midline. Dlp mutants do show genetic interactions with Slit and Robo in lateral fascicle formation. In addition, simultaneous loss of Dlp and Sdc demonstrates an important role for Dlp in midline repulsion, reminiscent of the functional overlap between Robo receptors. A comparison of HSPG distribution reveals a pattern that leaves midline proximal axons with relatively little Dlp. Finally, the loss of Dlp alters Slit distribution distal but not proximal to the midline, suggesting that distinct yet overlapping pattern of HSPG expression provides a spatial system that regulates axon guidance decisions. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 608–618, 2011

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