Abstract
Heparan sulfate (HS) proteoglycans are ubiquitous components of the extracellular matrix and plasma membrane of metazoans. The sulfation pattern of the HS glycosaminoglycan chain is characteristic for each tissue and changes during development. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes catalyze N-deacetylation and N-sulfation during HS biosynthesis and have a key role in designing the sulfation pattern. We here report on the presence of five NDST genes in zebrafish. Zebrafish ndst1a, ndst1b, ndst2a and ndst2b represent duplicated mammalian orthologues of NDST1 and NDST2 that arose through teleost specific genome duplication. Interestingly, the single zebrafish orthologue ndst3, is equally similar to tetrapod Ndst3 and Ndst4. It is likely that a local duplication in the common ancestor of lobe-finned fish and tetrapods gave rise to these two genes. All zebrafish Ndst genes showed distinct but partially overlapping expression patterns during embryonic development. Morpholino knockdown of ndst1b resulted in delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length, resembling some of the features of the Ndst1 mouse knockout.
Highlights
Heparan sulfate (HS) proteoglycans are found abundantly in basement membranes and on cell surfaces, where they function as co-receptors, store growth factors and participate in the generation of morphogen gradients [1]
Among the five zebrafish Ndsts, two of the proteins were found to be most similar to the NDST1s and were named Ndst1a and Ndst1b, while two of the others showed most similarity to the NDST2s and were named Ndst2a and Ndst2b
Comparing the amino acid sequences, zebrafish Ndst1b has slightly lower identity to other vertebrate NDST1 enzymes than Ndst1a (65–74% amino acid sequence identity compared to 73–81%)
Summary
Heparan sulfate (HS) proteoglycans are found abundantly in basement membranes and on cell surfaces, where they function as co-receptors, store growth factors and participate in the generation of morphogen gradients [1]. The HS chains, covalently attached to different proteoglycan core proteins, display varying sulfation patterns in different cells and tissues [2,3,4,5], with very little variation between individuals [2]. This implicates that HS biosynthesis is a highly regulated process, and reflects the requirement for specific HS sulfation patterns in different biological processes. Zebrafish express an even higher number of heparan sulfate biosynthetic enzymes. We show that reduced expression of one of the genes, ndst1b, results in delayed development, craniofacial cartilage abnormalities as well as shortened body and pectoral fin length
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