Differential sulfations and epimerization define heparan sulfate specificity in nervous system development

Hannes E. Buelow, Oliver Hobert

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

Heparan sulfate proteoglycans (HSPG) are components of the extracellular matrix through which axons navigate to reach their targets. The heparan sulfate (HS) side chains of HSPGs show complex and differentially regulated patterns of secondary modifications, including sulfations of distinct hydroxyl groups and epimerization of an asymmetric carbon atom. These modifications endow the HSPG-containing extracellular matrix with the potential to code for an enormous molecular diversity. Attempting to decode this diversity, we analyzed C. elegans animals lacking three HS-modifying enzymes, glucuronyl C5-epimerase, heparan 6O-sulfotransferase, and 2O-sulfotransferase. Each of the mutant animals exhibit distinct as well as overlapping axonal and cellular guidance defects in specific neuron classes. We have linked individual HS modifications to two specific guidance systems, the sax-3/Robo and kal-1/Anosmin-1 systems, whose activity is dependent on different HS modifications in different cellular contexts. Our results demonstrate that the molecular diversity in HS encodes information that is crucial for different aspects of neuronal development.

Original languageEnglish (US)
Pages (from-to)723-736
Number of pages14
JournalNeuron
Volume41
Issue number5
DOIs
StatePublished - Mar 4 2004
Externally publishedYes

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Heparitin Sulfate
Nervous System
Heparan Sulfate Proteoglycans
Sulfotransferases
Extracellular Matrix
Racemases and Epimerases
Hydroxyl Radical
Axons
Carbon
Neurons
Enzymes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. / Buelow, Hannes E.; Hobert, Oliver.

In: Neuron, Vol. 41, No. 5, 04.03.2004, p. 723-736.

Research output: Contribution to journalArticle

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