Role of heparan sulfate-2-O-sulfotransferase in the mouse.

Abstract

Heparan sulfate (HS) is a long unbranched polysaccharide found covalently attached to various proteins at the cell surface and in the extracellular matrix. It plays a central role in embryonic development and cellular function by modulating the activities of an extensive range of growth factors and morphogens. HS 2-O-sulfotransferase (Hs2st) occupies a critical position in the succession of enzymes responsible for the biosynthesis of HS, catalysing the transfer of sulfate to the C2-position of selected hexuronic acid residues within the nascent HS chain. Previous studies have concluded that 2-O-sulfation of HS is essential for it to cooperate in many growth factor/receptor interactions. Surprisingly therefore, embryos lacking functional Hs2st survive until birth, but die perinatally, suffering complete failure to form kidneys. However, this rather late lethality belies a more intricate involvement of 2-O-sulfated HS during development. The purpose of this review is to summarise the requirements for 2-O-sulfated HS during mouse development, at the morphological and molecular level. The implications that altered HS structure may have on growth factor/receptor signalling in vivo will be discussed.