Heparan sulfate proteoglycans: a sugar code for vertebrate development?

Heparan sulfate proteoglycans (HSPGs) have long been implicated in a wide range of cell-cell signaling and cell-matrix interactions, both in vitro and in vivo in invertebrate models. Although many of the genes that encode HSPG core proteins and the biosynthetic enzymes that generate and modify HSPG sugar chains have not yet been analyzed by genetics in vertebrates, recent studies have shown that HSPGs do indeed mediate a wide range of functions in early vertebrate development, for example during left-right patterning and in cardiovascular and neural development. Here, we provide a comprehensive overview of the various roles of HSPGs in these systems and explore the concept of an instructive heparan sulfate sugar code for modulating vertebrate development.