Differential expression of heparan sulfate 6‐O‐sulfotransferase isoforms in the mouse embryo suggests distinctive roles during organogenesis

Abstract

Heparan sulfate (HS) interactions with secreted morphogens such as fibroblast growth factors, hedgehogs, and Wnts are essential for embryonic development. Formation of biologically relevant HS structures is a result of the coordinated action of various biosynthetic enzymes. HS 6-O-sulfotransferases (6OST) catalyze the transfer of sulfate groups to the 6-O position of glucosamine residues in HS. Three 6OST isoforms have been described in the mouse; however, little is known about their role in generating specific HS protein-binding sequences, expression pattern, and function in vivo. To gain insights into the distribution of these isoforms and their potential role in development, we mapped 6OST1-3 gene expression during mouse organogenesis. We report dynamic expression of these isoforms with striking differences in tissue distribution in many developing organs. We show that 6OST transcripts are differentially expressed in several sites where heparin-binding growth factors are critical for development. 6OST1 is predominantly transcribed in epithelial and neural-derived tissues, whereas 6OST2 is more mesenchymal. 6OST3 appears at later stages and in a more restricted manner. The patterns reported here strongly suggest that the HS structures modified by these enzymes have different roles in growth factor-induced developmental processes.