Abstract
Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans are abundant on the cell surface and in the extracellular matrix and have important functions in matrix structure, cell-matrix interaction and signaling. The DS epimerases 1 and 2, encoded by Dse and Dsel, respectively, convert CS to a CS/DS hybrid chain, which is structurally and conformationally richer than CS, favouring interaction with matrix proteins and growth factors. We recently showed that Xenopus Dse is essential for the migration of neural crest cells by allowing cell surface CS/DS proteoglycans to adhere to fibronectin. Here we investigate the expression of Dse and Dsel in Xenopus embryos. We show that both genes are maternally expressed and exhibit partially overlapping activity in the eyes, brain, trigeminal ganglia, neural crest, adenohypophysis, sclerotome, and dorsal endoderm. Dse is specifically expressed in the epidermis, anterior surface ectoderm, spinal nerves, notochord and dermatome, whereas Dsel mRNA alone is transcribed in the spinal cord, epibranchial ganglia, prechordal mesendoderm and myotome. The expression of the two genes coincides with sites of cell differentiation in the epidermis and neural tissue. Several expression domains can be linked to previously reported phenotypes of knockout mice and clinical manifestations, such as the Musculocontractural Ehlers-Danlos syndrome and psychiatric disorders.
Highlights
Chondroitin sulfate (CS)/dermatan sulfate (DS) is a linear polysaccharide that is covalently attached to core proteins of proteoglycans and widely distributed both at the cell surface and in the extracellular matrix [1, 2]
At the amino acid level, their identities are 94% (DS-epi1 encoded by Dse) and 96% (DS-epi2 encoded by Dsel) [16]
Three amino acids in the epimerase domain that are required for its catalytic activity in human DS-epi1 (H205, Y261, H450; [27]) are conserved in each homeologous copy of the X. laevis DS-epi1 and DS-epi2 enzymes
Summary
Chondroitin sulfate (CS)/dermatan sulfate (DS) is a linear polysaccharide that is covalently attached to core proteins of proteoglycans and widely distributed both at the cell surface and in the extracellular matrix [1, 2]. CS/DS occurs in many invertebrates and vertebrates [3] and is involved in a range of biological functions, including the upbuilding of the extracellular matrix, cell signaling, wound healing, regeneration, and anti-coagulation [4, 5]. CS/DS is composed of alternating units of a hexuronic acid, i.e. either D-glucuronic acid (GlcA) or L-iduronic acid (IdoA), and the aminosugar N-acetyl-D-galactosamine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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