Abstract
Ubiquitously found in the extracellular matrix and attached to the surface of most cells, glycosaminoglycans (GAGs) mediate many intercellular interactions. Originally described in 1889 as the primary carbohydrate in cartilage and then in 1916 as a coagulation inhibitor from liver, various GAGs have since been identified as key regulators of normal physiology. GAGs are critical mediators of differentiation, migration, tissue morphogenesis, and organogenesis during embryonic development. While GAGs are simple polysaccharide chains, many GAGs acquire a considerable degree of complexity by extensive modifications involving sulfation and epimerization. Embryos that lack specific GAG modifying enzymes have distinct developmental defects, illuminating the importance of GAG complexity. Revealing how these complex molecules specifically function in the embryo has often required additional approaches, the results of which suggest that GAG modifications might instructively mediate embryonic development.