TY - JOUR
T1 - Differential sulfations and epimerization define heparan sulfate specificity in nervous system development
AU - Bülow, Hannes E.
AU - Hobert, Oliver
N1 - Funding Information:
We thank the CGC and various C. elegans researchers for providing strains and markers, the C. elegans knockout consortium in Oklahoma and the National Bioresource Project in Japan lead by Shohei Mitani for providing deletion mutants, Katherine Berry for communicating results on nerve ring patterning, Karl Johnson and David Van Vactor for comments and communicating results prior to publication, and Harald Hutter, Patricia Bernisone, Tarja Kinnunen, Jeremy Turnbull, Tom Jessell, Iva Greenwald, and members of the Hobert lab for comments on the manuscript. We thank Eric Salazar and Jan Philipp Kruse for constructing strains and Qi Chen for expert technical assistance. This work was funded by the HFSPO and the McKnight, Irma T. Hirschl, and Rita Allen Foundations.
PY - 2004/3/4
Y1 - 2004/3/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S0896-6273(04)00084-4
DO - 10.1016/S0896-6273(04)00084-4
M3 - Article
C2 - 15003172
AN - SCOPUS:2642542826
SN - 0896-6273
VL - 41
SP - 723
EP - 736
JO - Neuron
JF - Neuron
IS - 5
ER -