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On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis

Holmborn, Katarina ; Habicher, Judith ; Kasza, Zsolt ; Eriksson, Anna S ; Filipek-Gorniok, Beata ; Gopal, Sandeep LU orcid ; Couchman, John R ; Ahlberg, Per E ; Wiweger, Malgorzata and Spillmann, Dorothe , et al. (2012) In The Journal of biological chemistry 287(40). p.16-33905
Abstract

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 because of 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, whereas these mutants still were capable of synthesizing 50% of the HS... (More)

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 because of 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, whereas 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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alleles, Animals, Cartilage/metabolism, Chondroitin Sulfates/chemistry, Crosses, Genetic, Disease Progression, Female, Gene Expression Regulation, Developmental, Genotype, Heparitin Sulfate/chemistry, Male, Microscopy, Confocal/methods, Microscopy, Electron, Transmission/methods, Models, Biological, Morphogenesis, Mutation, Pharynx/pathology, Zebrafish
in
The Journal of biological chemistry
volume
287
issue
40
pages
16 - 33905
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:22869369
  • scopus:84866941195
ISSN
1083-351X
DOI
10.1074/jbc.M112.401646
language
English
LU publication?
no
id
84f19ea9-43b9-4801-9567-b83b9fb0669c
date added to LUP
2021-10-25 13:21:27
date last changed
2024-06-16 22:35:07
@article{84f19ea9-43b9-4801-9567-b83b9fb0669c,
  abstract     = {{<p>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 because of 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, whereas 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.</p>}},
  author       = {{Holmborn, Katarina and Habicher, Judith and Kasza, Zsolt and Eriksson, Anna S and Filipek-Gorniok, Beata and Gopal, Sandeep and Couchman, John R and Ahlberg, Per E and Wiweger, Malgorzata and Spillmann, Dorothe and Kreuger, Johan and Ledin, Johan}},
  issn         = {{1083-351X}},
  keywords     = {{Alleles; Animals; Cartilage/metabolism; Chondroitin Sulfates/chemistry; Crosses, Genetic; Disease Progression; Female; Gene Expression Regulation, Developmental; Genotype; Heparitin Sulfate/chemistry; Male; Microscopy, Confocal/methods; Microscopy, Electron, Transmission/methods; Models, Biological; Morphogenesis; Mutation; Pharynx/pathology; Zebrafish}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{40}},
  pages        = {{16--33905}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{The Journal of biological chemistry}},
  title        = {{On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis}},
  url          = {{http://dx.doi.org/10.1074/jbc.M112.401646}},
  doi          = {{10.1074/jbc.M112.401646}},
  volume       = {{287}},
  year         = {{2012}},
}