A network of HSPG core proteins and HS modifying enzymes regulates netrin-dependent guidance of D-type motor neurons in Caenorhabditis elegans

Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range...

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Bibliographic Details
Published in:PloS one 2013-09, Vol.8 (9), p.e74908-e74908
Main Authors: Gysi, Stephan, Rhiner, Christa, Flibotte, Stephane, Moerman, Donald G, Hengartner, Michael O
Format: Article
Language:English
Subjects:
Animals
Axon guidance
Axons
Caenorhabditis elegans
Caenorhabditis elegans - cytology
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - metabolism
Cancer
Cellular structure
Chains
Defects
Derepression
Dosage compensation
Drosophila
Enzymes
Gene dosage
Genes
Genetic analysis
Heparan sulfate
Heparan sulfate proteoglycans
Heparan Sulfate Proteoglycans - metabolism
Heparitin Sulfate - metabolism
Insects
Life sciences
Ligands
Motor neurons
Motor Neurons - cytology
Motor Neurons - metabolism
Mutants
Mutation
Nematodes
Nerve Tissue Proteins - metabolism
Nervous system
Netrins
Neurons
Neurosciences
Phosphatase
Proteins
Proteoglycans
Sugar
Sulfates
Syndecan
Worms
Zoology
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Summary:Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0074908