Roles of sialoglycans in vertebrate development

In vertebrates, sialic acids are the terminal sugars of many glycan structures presented by glycolipids, glycoproteins and proteoglycans on the cell surface, in the extracellular matrix, and in bodily fluids. Due to their negative charge, they shape molecular interactions between cells as well as interactions with and within the microenvironment. Strategies to study the numerous and diverse functions of sialoglycans in health and disease range from global sialic acid deletions to the targeting of specific sialoglycan biosynthesis pathways in individual cell types or organs. Some of these approaches reveal fundamental, some rather subtle, or no developmental functions of specific sialoglycans. However, many of the available models aim to investigate selected aspects such as immune cell or tumor development (to name just two prominent examples), and most sialylation pathways remain severely understudied. Despite many excellent reviews on specific pathways, molecular entities, or disease- and organ-specific functions (as, e.g., assembled in this thematic series on sialic acids) a comprehensive current overview of the developmental roles of sialoglycans seems to be missing. This review tries to close this gap, but in light of the expert coverage of sialylated glycosphingolipids (gangliosides) in this series (1), we focus on the insights into the developmental roles of sialoglycans gained by approaches targeting sialylation per se or pathways affecting sialylation of either specifically glycoproteins or glycoproteins and glycolipids alike. In addition to the consequences of manipulations of global sialylation, particular emphasis will be on the developmental roles of polysialic acid in the brain and other organs.