title: Chondroitin-4-sulfation negatively regulates axonal guidance and growth.
abstract: Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated chondroitin sulfate GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings show that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function.
authors.affiliation: Developmental Neurobiology Section, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Katagiri
authors.forename: Thomas E
authors.initials: TE
authors.lastname: McCann
authors.forename: Edward
authors.initials: E
authors.lastname: Unsworth
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.forename: Zu-Xi
authors.initials: ZX
authors.lastname: Yu
authors.forename: Fei
authors.initials: F
authors.lastname: Tan
authors.forename: Lizzie
authors.initials: L
authors.lastname: Santiago
authors.forename: Edward M
authors.initials: EM
authors.lastname: Mills
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Aviva J
authors.initials: AJ
authors.lastname: Symes
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Geller