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On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis
Holmborn, K., Habicher, J., Kasza, Z., Eriksson, A.S., Filipek-Gorniok, B., Gopal, S., Couchman, J.R., Ahlberg, P., Wiweger, M., Spillman, D., Kreuger, J., and Ledin, J.
Date:
2012
Source:
The Journal of biological chemistry
287(40):
33905-33916 (Journal)
Holmborn, K., Habicher, J., Kasza, Z., Eriksson, A.S., Filipek-Gorniok, B., Gopal, S., Couchman, J.R., Ahlberg, P., Wiweger, M., Spillman, D., Kreuger, J., and Ledin, J. (2012) On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis. The Journal of biological chemistry. 287(40):33905-33916.
The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in
the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis
of both HS and CS due to defective formation of the common proteoglycan linkage tetrasaccharide were analyzed, along with
ext2 and extl3 mutants, predicted to have defective HS polymerization. Notably, the effects on HS and CS biosynthesis in the
respective mutant strains were shown to differ from what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis
of CS was shown to be virtually abolished while these mutants still were capable of synthesizing 50% of the HS produced in
control larvae. extl3 and ext2 mutants on the other hand were shown to synthesize reduced amounts of hypersulfated HS. Further,
extl3 mutants produced higher levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2
resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS
ratio. A characterization of the pharyngeal cartilage element morphologies in the single mutant strains, as well as in ext2;uxs1
double mutants, was conducted. A correlation between HS and CS production and phenotypes was found, such that impaired HS
biosynthesis was shown to affect chondrocyte intercalation, whereas impaired CS biosynthesis inhibited formation of the extracellular
matrix surrounding chondrocytes.