Chondroitin

Chondroitin sulfate/dermatan sulfate hybrid chains in the development of cerebellum:Spatiotemporal regulation of the expression of critical disulfated disaccharides by specific sulfotransferases.

Mitsunaga C, Mikami T, Mizumoto S, Fukuda J, Sugahara K.

Department of Biochemistry, Kobe Pharmaceutical University, Kobe, Hyogo 658-8558.

Chondroitin sulfate/dermatan sulfate (CS/DS) chains regulate the development of the central nervous system in vertebrates. Previously, we demonstrated that CS/DS hybrid chains from embryonic pig brain exhibit neuritogenic and growth factor-binding activities, which depended on their iduronic acid (IdoUA) content defining DS-like structure. To elucidate the distribution of such functional sugar chains during the brain's development, in situ hybridization was performed to examine expression of three CS/DS GalNAc 4-O-sulfotransferases, D4ST-1, C4ST-1, and C4ST-2, and a single uronyl 2-O-sulfotransferase (UST), involved in the biosynthesis of DS in addition to CS intermediates. C4ST-1 and C4ST-2 were ubiquitously expressed in the postnatal mouse brain, whereas the expression of D4ST-1 and UST was restricted in the developing cerebellum and culminated at P14 as shown by RT-PCR analysis. In situ analysis of the disaccharides of CS/DS in brain sections revealed that the concentration of CS/DS increases 2-fold during development (P7 to 7W). The proportions of DS-specific, principal disaccharides, iA [IdoUA-GalNAc(4-O-sulfate)] and iB [IdoUA(2-O-sulfate)-GalNAc(4-O-sulfate)], produced by the sequential actions of D4ST-1 and UST, were higher in the CS/DS chains from cerebellum than those from whole brain sections. A dramatic (10-fold) increase in the proportion of iB during development was noteworthy. In contrast, D/iD [GlcUA/IdoUA(2-O-sulfate)-GalNAc(6-O-sulfate)] and E/iE [GlcUA/IdoUA-GalNAc(4, 6-O-disulfate)] decreased to 50 and 30%, respectively, in the developing cerebellum. These results suggest that the IdoUA-containing iA and iB units along with D/iD and E/iE units in the CS/DS hybrid play important roles in the formation of the cerebellar neural network during postnatal brain development.

PMID: 16702220 [PubMed - as supplied by publisher]

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