Structural and functional changes of sulfated glycosaminoglycans in Xenopus laevis during embryogenesis

Abstract

Xenopus laevis is an excellent animal for analyzing early vertebrate development. Various effects of glycosaminoglycans (GAGs) on growth factor-related cellular events during embryogenesis have been demonstrated in Xenopus. To elucidate the relationship between alterations in fine structure and changes in the specificity of growth factor binding during Xenopus development, heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) chains were isolated at four different embryonic stages and their structure and growth factor-binding capacities were compared. The total amounts of both HS and CS/DS chains decreased from the pre-midblastula transition to the gastrula stage, but increased exponentially during the following developmental stages. The length of HS chains was not significantly affected by development, whereas that of CS/DS chains increased with development. The disaccharide composition of GAGs in embryos also changed during development. The degree of sulfation of the HS chains gradually decreased with development. The predominant sulfation position in the CS/DS chains shifted from C4 to C6 of GalNAc during embryogenesis. Growth factor-binding experiments using a BIAcore system demonstrated that GAGs bound growth factors including fibroblast growth factors-1 and -2, midkine, and pleiotrophin, with comparable affinities. These affinities significantly varied during development, although the correlation between the structural alterations of GAGs and the change in the ability to bind growth factors remains to be clarified. The expression of saccharide sequences, which specifically interact with a growth factor, might be regulated during development.

A case study: Glycosaminoglycan profiles of autologous chondrocyte implantation (ACI) tissue improve as the tissue matures

“…At 20 months the ACI biopsy had 0.37±0.1µg/mg and the cadaveric biopsies had 0.36±0.09µg/mg. These data compare well with previously published data for adult articular cartilage 8,17,22 .…”

“…For both the ACI repair tissue and control tissues, analysis of the terminal sugars of CS identified low levels of GalNAc and GalNAc6S but no GalNAc4,6S ( Figure 3B). Previous studies, including our own, have not detected GalNAc4,6S 8,17,22 .…”

“…GAGs in articular cartilage change as a function of development, age and disease [16][17][18][19][20][21][22][23] . In adult cartilage, 50-80% of GAGs are CS chains which are composed of glucuronic acid and N-acetylgalactosamine monosaccharides.…”

“…During development, chondroitin sulphation is thought to be tightly controlled both spatially and temporally 17 . During embryogenesis CS chains are exclusively C6S.…”

Analysis of the structure and neuritogenic activity of chondroitin sulfate/dermatan sulfate hybrid chains from porcine fetal membranes

“…DS, which mainly consists of IdoA-GalNAc(4-O-sulfate) disaccharide units, promotes the binding of FGF-7 to a FGF receptor and the cell proliferation of keratinocytes [6], and also acts as a co-receptor 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 18 required for the formation of an active HGF signaling complex [34,35]. The DS-like structure in Xenopus CS/DS was reported to be involved in its binding to FGF-1 [36].…”