title: Chondroitin / dermatan sulfate modification enzymes in zebrafish development.
abstract: 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.
authors: Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Judith
authors: J
authors: Habicher
authors: Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Tatjana
authors: T
authors: Haitina
authors: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Inger
authors: I
authors: Eriksson
authors: Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Katarina
authors: K
authors: Holmborn
authors: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Tabea
authors: T
authors: Dierker
authors: Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Per E
authors: PE
authors: Ahlberg
authors: Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Johan
authors: J
authors: Ledin
mesh_terms: D000818:Animals; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003871:Dermatan Sulfate / Q000031:analogs & derivatives* / Q000378:metabolism; D047108:Embryonic Development; D006497:Heparan Sulfate / Q000378:metabolism; D017403:In Situ Hybridization; D010802:Phylogeny; D015238:Sulfotransferases / Q000378:metabolism*; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D015238:Sulfotransferases; D029961:Zebrafish Proteins; C069524:dermatan sulfate chondroitin sulfate; C019893:chondroitin 4-sulfotransferase