Extracellular Sugar Modifications Provide Instructive and Cell-Specific Information for Axon-Guidance Choices

Hannes E. Bülow, Nartono Tjoe, Robert A. Townley, Dominic Didiano, Toin H. van Kuppevelt, Oliver Hobert

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Heparan sulfates (HSs) are extraordinarily complex extracellular sugar molecules that are critical components of multiple signaling systems controlling neuronal development [1-3]. The molecular complexity of HSs arises through a series of specific modifications, including sulfations of sugar residues and epimerizations of their glucuronic acid moieties. The modifications are introduced nonuniformly along protein-attached HS polysaccharide chains by specific enzymes [4]. Genetic analysis has demonstrated the importance of specific HS-modification patterns for correct neuronal development [2, 3]. However, it remains unclear whether HS modifications provide a merely permissive substrate or whether they provide instructive patterning information during development. We show here with single-cell resolution that highly stereotyped motor axon projections in C. elegans depend on specific HS-modification patterns. By manipulating extracellular HS-modification patterns, we can cell specifically reroute axons, indicating that HS modifications are instructive. This axonal rerouting is dependent on the HS core protein lon-2/glypican and both the axon guidance cue slt-1/Slit and its receptor eva-1. These observations suggest that a changed sugar environment instructs slt-1/Slit-dependent signaling via eva-1 to redirect axons. Our experiments provide genetic in vivo evidence for the "HS code" hypothesis which posits that specific combinations of HS modifications provide specific and instructive information to mediate the specificity of ligand/receptor interactions [3, 5, 6].

Original languageEnglish (US)
Pages (from-to)1978-1985
Number of pages8
JournalCurrent Biology
Issue number24
StatePublished - Dec 23 2008



ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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