Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans [Developmental and Behavioral Genetics]

Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans. We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts. Double mutant analyses reveal distinct redundancies among HSPGs for different migration events, and different cellular migrations require distinct heparan sulfate modification patterns. Our studies reveal that the transmembrane HSPG SDN-1/Syndecan functions within the migrating cell to promote cellular migrations, while the GPI-linked LON-2/Glypican functions cell nonautonomously to establish the final cellular position. Genetic analyses with the Wnt-signaling system show that (1) a given HSPG can act with different Wnts and Frizzled receptors, and that (2) a given Wnt/Frizzled pair acts with different HSPGs in a context-dependent manner. Lastly, we find that distinct HSPG and Wn...

Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Authors: Saied-Santiago, K., Townley, R. A., Attonito, J. D., da Cunha, D. S., Diaz-Balzac, C. A., Tecle, E., Bulow, H. E. Tags: Developmental and Behavioral Genetics Source Type: research