RRC ID 422
Author Bülow HE, Hobert O.
Title Differential sulfations and epimerization define heparan sulfate specificity in nervous system development.
Journal Neuron
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.
Volume 41(5)
Pages 723-36
Published 2004-3-4
DOI 10.1016/s0896-6273(04)00084-4
PII S0896627304000844
PMID 15003172
MeSH Amino Acid Sequence Animals Caenorhabditis elegans Gene Expression Regulation, Developmental / physiology Heparitin Sulfate / genetics* Heparitin Sulfate / metabolism* Molecular Sequence Data Nervous System / growth & development* Neurons / physiology Racemases and Epimerases / genetics* Racemases and Epimerases / metabolism*
IF 14.415
Times Cited 188
WOS Category NEUROSCIENCES
Resource
C.elegans tm472