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

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

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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
Volume18
Issue number24
DOIs
StatePublished - Dec 23 2008

Fingerprint

Heparitin Sulfate
axons
Sugars
sugars
cells
Axons
heparan sulfate
Axon Guidance
Glypicans
Glucuronic Acid
glucuronic acid
receptors
Cues
Polysaccharides
genetic techniques and protocols
Proteins
polysaccharides
proteins
Ligands

Keywords

  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Extracellular Sugar Modifications Provide Instructive and Cell-Specific Information for Axon-Guidance Choices. / Buelow, Hannes E.; Tjoe, Nartono; Townley, Robert A.; Didiano, Dominic; van Kuppevelt, Toin H.; Hobert, Oliver.

In: Current Biology, Vol. 18, No. 24, 23.12.2008, p. 1978-1985.

Research output: Contribution to journalArticle

Buelow, Hannes E. ; Tjoe, Nartono ; Townley, Robert A. ; Didiano, Dominic ; van Kuppevelt, Toin H. ; Hobert, Oliver. / Extracellular Sugar Modifications Provide Instructive and Cell-Specific Information for Axon-Guidance Choices. In: Current Biology. 2008 ; Vol. 18, No. 24. pp. 1978-1985.
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