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

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.

A girl with developmental delay, ataxia, cranial nerve palsies, severe respiratory problems in infancy—Expanding NDST1 syndrome

“…We present a girl with neurodevelopmental, morphological and growth differences in keeping with previously reported individuals also having biallelic mutations in NDST1 , and the zebrafish morpholino knockdown model [Filipek‐Górniok et al, ]. Not previously reported are the cranial nerve dysfunctions, the bifid uvula, and the respiratory problems of infancy.…”

“…In terms of model organism research, ndst1b (orthologous to NDST1) morpholino knockdown in zebrafish causes delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length [Filipek‐Górniok et al, ]. Ndst1 has been extensively studied in mice.…”

“…No humans with homozygous null mutations are known. ndst1b (orthologous to NDST1) morpholino knockdown in zebrafish (Danio rerio) causes delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length [Filipek‐Górniok et al, ]. Ndst1 homozygous null mice have a craniofacial phenotype and die within the first 10 h of life of respiratory failure [Fan et al, ; Ringvall and Kjellen, 2010].…”

Association study of NDST3 gene for schizophrenia, bipolar disorder, major depressive disorder in the Han Chinese population

“…N‐deacetylase/N‐sulfotransferase (heparin glucosaminyl) 3( NDST3 ) gene is a member of the NDST1‐NDST4 family which encodes NDST isozymes (Aikawa et al, ; Eriksson et al, ; Hashimoto et al, ; Kusche‐Gullberg et al, ). 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 (Filipek‐Górniok et al, ). NDST is a bifunctional enzyme, which removes acetyl groups from GlcNAc residues and replaces them with sulfate groups (Filipek‐Górniok et al, ).…”

Morphogenesis and differentiation of embryonic vascular smooth muscle cells in zebrafish

“…1A, 173 C, E, G, I, and K). Specifically, foxc1b is expressed in the region of the aortic arches, jaw, 174 ceratohyal (Schilling et al, 1996;Knight, 2003;Filipek-Górniok et al, 2015;Xu et al, 2018) and 175 in the periocular mesenchyme in the ventral head. Furthermore, foxc1b mRNA expression 176 overlaps with foxc1b:EGFP transgenic expression in the ventral aorta, aortic arch arteries, and 177 ceratohyal at 2 and 4 dpf, suggesting EGFP in the transgenic fish line mimics endogenous mRNA 178 expression ( Fig.…”