Expression of glycosaminoglycan epitopes during zebrafish skeletogenesis

Hayes, Anthony Joseph; Mitchell, Ruth; Bashford, Andrew; Reynolds, Scott B.; Caterson, Bruce; Hammond, Chrissy L.

doi:10.1002/dvdy.23970

Cited by 8 publications

(7 citation statements)

References 82 publications

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“…7 ). These components can further be detected in most cartilage and bone structures by antibodies recognizing CS/DS motifs in zebrafish larvae at 4 dpf and 8 dpf [ 34 ] and similar proportions of different CS/DS disaccharides is found in vertebral CS/DS during zebrafish ageing [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…CS/DS biosynthesis enzymes produce tissue specific structures during zebrafish development [ 34 ] presumably as a result of differential expression of CS/DS modification enzymes (Figs. 3 – 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…Hayes and coworkers have used antibodies recognizing CS/DS sulfation motifs to study zebrafish skeletogenesis, and describe non-sulfated disaccharides and disaccharides with sulfate groups at C-4 and C-6 positions ( Fig. 1 ), but also more subtle changes in sulfation pattern indicating dynamic control of CS/DS biosynthesis during development [ 34 ]. Expression of CS/DS modification enzymes during zebrafish embryonic development has not been systematically studied but a study of zebrafish c hst11 ( C4ST-1 ) shows persistent expression in somites and brain, and transient expression in the pectoral fins [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development

et al. 2015

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Chondroitin/dermatan sulfate (CS/DS) proteoglycans consist of unbranched sulfated polysaccharide chains of repeating GalNAc-GlcA/IdoA disaccharide units, attached to serine residues on specific proteins. The CS/DS proteoglycans are abundant in the extracellular matrix where they have essential functions in tissue development and homeostasis. In this report a phylogenetic analysis of vertebrate genes coding for the enzymes that modify CS/DS is presented. We identify single orthologous genes in the zebrafish genome for the sulfotransferases chst7, chst11, chst13, chst14, chst15 and ust and the epimerase dse. In contrast, two copies were found for mammalian sulfotransferases CHST3 and CHST12 and the epimerase DSEL, named chst3a and chst3b, chst12a and chst12b, dsela and dselb, respectively. Expression of CS/DS modification enzymes is spatially and temporally regulated with a large variation between different genes. We found that CS/DS 4-O-sulfotransferases and 6-O-sulfotransferases as well as CS/DS epimerases show a strong and partly overlapping expression, whereas the expression is restricted for enzymes with ability to synthesize di-sulfated disaccharides. A structural analysis further showed that CS/DS sulfation increases during embryonic development mainly due to synthesis of 4-O-sulfated GalNAc while the proportion of 6-O-sulfated GalNAc increases in later developmental stages. Di-sulfated GalNAc synthesized by Chst15 and 2-O-sulfated GlcA/IdoA synthesized by Ust are rare, in accordance with the restricted expression of these enzymes. We also compared CS/DS composition with that of heparan sulfate (HS). Notably, CS/DS biosynthesis in early zebrafish development is more dynamic than HS biosynthesis. Furthermore, HS contains disaccharides with more than one sulfate group, which are virtually absent in CS/DS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development

et al. 2015

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“…In adult zebrafish, CS and KS account for the majority of the total GAG content, with both being dynamically expressed during early development [50,51,52]. HS expression is high in the first 24 hours of life (~50%), but decreases as a proportion of total GAG content thereafter; whereas CS and KS increase throughout life [53].…”

Section: Discussionmentioning

confidence: 99%

Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis

et al. 2013

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Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking age-related changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.

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“…PGs, especially heparan sulfate (HS) and chondroitin sulfate (CS) PGs, are highly expressed in chondrocyte ECM and play a significant role in maturation of chondrocytes and endochondral skel- Fig. 2) [17][18][19][20]. CS and HS PGs can bind to a variety of molecules such as growth factors, chemokines, ECM proteins, and axon guidance molecules.…”

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confidence: 99%

Abnormal Proteoglycan Synthesis Due to Gene Defects Causes Skeletal Diseases with Overlapping Phenotypes

Taylan

Mäkitie

2016

Horm Metab Res

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In recent years, massively parallel sequencing technologies have helped us to identify novel disease genes and solve the mysteries behind rare diseases. Today, we know that some diseases with many overlapping and distinct clinical features, as presented in this review, can be caused by mutations in genes that encode enzymes playing crucial roles at different steps of the exact same pathway. In this review, we exclusively focused on 5 genes - ,, ,, and - that encode enzymes involved in the biosynthesis of the common tetrasaccharide linker region of proteoglycans and review the associated diseases, also referred to as linkeropathies, by summarizing the cases reported in literature. Since proteoglycans are essential macromolecules in development, signaling and homeostasis of many tissues and organs, mutations in these genes can affect many organs; including bone, cartilage, eyes, ears, heart, and skin. Short stature, developmental delay, facial dysmorphism, and skeletal dysplasias are some of the common features observed in patients with mutations in these genes. Among these genes, mutations cause a relatively distinct phenotype, the so-called spondyloocular syndrome, which is characterized by clinical presentation of a very severe childhood-onset primary osteoporosis, cataract, and hearing impairment. The full phenotype spectrum of diseases mentioned here is likely to expand with additional clinical reports and further molecular studies.

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Expression of glycosaminoglycan epitopes during zebrafish skeletogenesis

Cited by 8 publications

References 82 publications

Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development

Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development

Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis

Abnormal Proteoglycan Synthesis Due to Gene Defects Causes Skeletal Diseases with Overlapping Phenotypes

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