Heperan sulfate proteogycans regulate signaling, cell polarity and ligand diffusion during zebrafish lateral line development

Embryological development encompasses a fascinating collection of biological events somehow able to act jointly and precisely to give as a final product a welldeveloped viable organism, which can span from very basic to extremely complex animals. Understanding how individual cells can talk to their neighbors and establish their peculiar fates in a time- and space-dependent manner has intrigued the developmental biology field for ages. Signals among cells in a developing embryo are responsible for establishing such fates in a synchronized mode and this process is achieved mostly by strict feedbacks between cell-signaling pathways such Wnt, Fgf, Notch, BMP and Chemokines among others. I present a study on the functions of Heparan Sulfate Proteoglycans (HSPGs) during the zebrafish lateral line development. The lateral line is an excellent model to perform these studies as we have detailed knowledge on the signaling pathways involved in its development. HSPGs are extracellular glycoproteins with powerful, yet poorly understood, signaling modulating properties. I use the lateral line to dissect the regulation by HSPGs mainly on Wnt/β-catenin and Fgf signaling, two essential pathways during this developmental process. My data demonstrate that HSPGs are not only modulators but also target genes of the Wnt/β-catenin and Fgf signaling feedback. Furthermore, they are essential for Fgf signal transduction, migration and cell polarity. Also, I analyzed for the first time the role of a specific HSPG, glypican4, in lateral line development and iv discerned that this gene affects primordium migration non-cell-autonomously by inducing the formation of the muscles along the horizontal myoseptum, and controlling the proper orientation of the hair cells in the lateral line sensory organs, called neuromasts.