Gouignard Nadège, Schön Tanja, Holmgren Christian, Strate Ina, Taşöz Emirhan, Wetzel Franziska, Maccarana Marco, Pera Edgar M
Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, Lund, Sweden.
Department of Experimental Medical Science, Lund University, Lund, Sweden.
PLoS One. 2018 Jan 25;13(1):e0191751. doi: 10.1371/journal.pone.0191751. eCollection 2018.
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.
硫酸软骨素(CS)/硫酸皮肤素(DS)蛋白聚糖在细胞表面和细胞外基质中含量丰富,在基质结构、细胞-基质相互作用及信号传导中发挥重要作用。分别由Dse和Dsel编码的DS差向异构酶1和2将CS转化为CS/DS杂合链,其结构和构象比CS更丰富,有利于与基质蛋白和生长因子相互作用。我们最近发现,非洲爪蟾的Dse通过使细胞表面的CS/DS蛋白聚糖黏附于纤连蛋白,对神经嵴细胞的迁移至关重要。在此,我们研究了非洲爪蟾胚胎中Dse和Dsel的表达情况。我们发现这两个基因均为母源表达,且在眼睛、脑、三叉神经节、神经嵴、腺垂体、体节和背侧内胚层中表现出部分重叠的活性。Dse在表皮、前表面外胚层、脊神经、脊索和皮节中特异性表达,而单独的Dsel mRNA在脊髓、鳃上神经节、索前中胚层和肌节中转录。这两个基因的表达与表皮和神经组织中的细胞分化位点一致。几个表达域可与先前报道的基因敲除小鼠的表型及临床表现相关联,如肌肉挛缩性埃勒斯-当洛综合征和精神疾病。