Abstract
Heparan sulfate proteoglycans (HSPGs) are complex glycoproteins present ubiquitously at the cell surface and in the extracellular matrix. Heparan sulfate (HS) and HSPGs interact with a variety of growth factors, morphogens, extracellular matrix (ECM) proteins and proteases and thus play essential roles in controlling cell differentiation, tissue morphogenesis and homeostasis. The importance of HS and HSPGs has been highlighted by the findings that a number of human genetic disorders are associated with mutations in genes encoding for HSPGs or HS biosynthetic enzymes. The HS mediated interactions are often dependent on specific HS structures that arise from differential sulfation modifications to the sugar backbone during biosynthesis. The fine structure of HS varies tissue specifically, during development and in disease conditions but the regulation of HS biosynthesis is still not fully understood. Recent studies using genetic model organisms together with cell biological and biochemical approaches have indicated specific roles for heparan sulfotransferases in defined developmental pathways emphasizing the importance of specific HS structures during development.
