Hyaluronan: Genetic insights into the complex biology of a simple polysaccharide

It is appropriate that this review should appear in a volume dedicated to Mert Bernfield. Much of my interest in the cell biology of the extracellular matrix, particularly during development, echoes Mert's pioneering studies. His kind but provocative questioning during meetings is especially missed. The glycosaminoglycan hyaluronan is ubiquitous, and is especially abundant during embryogenesis. Hydrated matrices rich in hyaluronan expand the extracellular space, facilitating cell migration. The viscoelastic properties of hyaluronan are also essential for proper function of cartilage and joints. Recent understanding of hyaluronan biology has benefited from the identification of genes encoding hyaluronan synthases and hyaluronidases, genetic analysis of the roles of hyaluronan during development, elucidation of the biochemical mechanisms of hyaluronan synthesis, and by studies of human genetics and tumors. This review focuses on recent studies utilizing hyaluronan-deficient, gene targeted mice with null alleles for the principal source of hyaluronan during mid-gestation, hyaluronan synthase-2 (has-2).