The Ndst Gene Family in Zebrafish: Role of Ndst1b in Pharyngeal Arch Formation

<div><p>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 <i>N</i>-deacetylase/<i>N</i>-sulfotransferase (NDST) enzymes catalyze <i>N</i>-deacetylation and <i>N</i>-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 <i>ndst1a</i>, <i>ndst1b</i>, <i>ndst2a</i> and <i>ndst2b</i> represent duplicated mammalian orthologues of <i>NDST1</i> and <i>NDST2</i> that arose through teleost specific genome duplication. Interestingly, the single zebrafish orthologue <i>ndst3</i>, is equally similar to tetrapod <i>Ndst3</i> and <i>Ndst4</i>. 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 <i>ndst1b</i> resulted in delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length, resembling some of the features of the <i>Ndst1</i> mouse knockout.</p>