The role of glycosaminoglycan motifs in regulating neuronal growth, guidance and inhibition

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27 Dramatic changes in the expression of various 3OST and 6OST isoforms were observed in a spatiotemporal manner in developing zebrafish (192, 193). HS fine structure in the pineal gland showed differences when assessed in light versus dark conditions (194). The differential expression in development as well as changes in sulfotransferase expression due to environmental cues such as light implies that control of specific HS sulfation is important to normal development and neural function. The specificity of HS sulfation in determining their binding affinity for different isoforms of FGF has been investigated extensively. IdoA2S-GlcNS was found to increase the binding affinity of HS with basic FGF, and the affinity increased with increasing sulfation density (195). Sulfates seem to impart a defined structure to the HS microdomains, thus controlling their selectivity for binding to various ligands. Many such ligand receptor interactions like FGFFGFR play a crucial role in various CNS processes such as neural plate patterning, neurogenesis, gliogenesis, axonal pathfinding, and regeneration during injury. Further details on the role of FGFs in CNS can be found in the review by Guillemot et al. (196). Although several distinct roles have been proposed for HS- and CSmediated signaling, the existence of overlap in their CNS interactions cannot be excluded completely. In fact, crystallographic analysis of RPTPσ revealed a shared binding site for HS and CS (197). In fact, Coles et al. proposed that both HS and CS can bind to RPTPσ and still mediate their differential response on neurons (197). The computational model suggested that due to the difference in