Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation
Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation
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DOI：
10.1101/gad.11.14.1873
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发表时间：
1997-07-15
影响因子：
10.5
通讯作者：
Rosenfeld, MG
中科院分区：
文献类型：
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作者：
Andersen, B;Weinberg, WC;Rosenfeld, MG
在这里，我们报道了POU结构域基因SKIN-1a/I(SKN-1a/I/Epoc/Oct-11)和Tes-1(Tst-1/Oct-6/SCIP)在表皮中的作用，在表皮中，增殖的基底层角质形成细胞退出细胞周期，向基上迁移，并最终分化形成多层复层上皮。SKN-1a/I和Tst-1基因的表达与角质形成细胞在体内和体外的分化有关，而普遍存在的POU结构域因子Oct-1在增殖和有丝分裂后的角质形成细胞中都高表达。对SKN-1a/I基因缺失小鼠的分析表明，SKN-1a/I基因调节终末分化标记Clicrin的表达模式，并抑制编码表皮角质形成细胞损伤反应标记的基因的表达。虽然Tst-1基因缺失小鼠的表皮发育正常，但同时缺失SKN-1a/i和Tst-1基因的小鼠的表皮是增殖的，移植到无瘤小鼠身上时，未能抑制K14和Spr-1在基底上细胞中的表达。这表明SKN-1a/I和Tst-1在表皮中具有多余的功能。因此，至少有两个POU结构域基因SKN-1a/I和Tst-1在表皮角质形成细胞的正常发育和伤口愈合过程中发挥着截然不同且相互重叠的功能。
Here we report on investigation of the role of the POU domain genes Skin-1a/i (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where proliferating basal keratinocytes withdraw from the cell cycle, migrate suprabasally, and terminally differentiate to form a multilayered, stratified epithelium. The expression of the Skn-1a/i and Tst-1 genes is linked to keratinocyte differentiation in vivo and in vitro, whereas the ubiquitous POU domain factor Oct-1 is expressed highly in both proliferating and post-mitotic keratinocytes. Analysis of Skn-1a/i gene-deleted mice reveals that the Skn-1a/i gene modulates the pattern of expression of the terminal differentiation marker loricrin and inhibits expression of genes encoding markers of the epidermal keratinocyte wounding response. Although epidermis from Tst-1 gene-deleted mice develops normally, epidermis from mice deleted for both Skn-1a/i and Tst-1 is hyperplastic and fails to suppress expression of K14 and Spr-1 in suprabasal cells when transplanted onto athymic mice. This suggests that Skn-1a/i and Tst-1 serve redundant functions in epidermis. Therefore, at least two POU domain genes, Skn-1a/i and Tst-1, serve both distinct and overlapping functions to regulate differentiation of epidermal keratinocytes during normal development and wound healing.