Int. J. Dev. Biol. 46: 267 - 278 (2002)
Developmental roles of heparan sulfate proteoglycans: a comparative review in Drosophila, mouse and human
Published: 1 May 2002
Abstract
In recent years, progress in the fields of development and proteoglycan biology have produced converging evidence of the role of proteoglycans in morphogenesis. Numerous studies have demonstrated that proteoglycans are involved in several distinct morphogenetic pathways upon which they act at different levels. In particular, proteoglycans can determine the generation of morphogen gradients and be required for their signal transduction. The surface of most cells and the extracellular matrix are decorated by heparan sulfates which are the most common glycosaminoglycans, normally present as heparan sulfate proteoglycans. Considerable structural heterogeneity is generated in proteoglycans by the biosynthetic modification of their heparan sulfate chains as well as by the diverse nature of their different core proteins. This heterogeneity provides an impressive potential for protein-protein and protein-carbohydrate interactions, and can partly explain the diversity of proteoglycan involvement in different morphogenetic pathways. In this review, we summarize the current knowledge about mutations affecting heparan sulfate proteoglycans that influence the function of growth factor pathways essential for tissue assembly, differentiation and development. The comparison of data obtained in Drosophila, rodents and humans reveals that mutations affecting the proteoglycan core proteins or one of the biosynthetic enzymes of their heparan sulfate chains have profound effects on growth and morphogenesis. Further research will complete the picture, but current evidence shows that at the very least, heparan sulfate proteoglycans need to be counted as legitimate elements of morphogenetic pathways that have been maintained throughout evolution as determinant mechanisms of pattern formation.