Ridanpää M, Fodde R, Kielman M
Department of Human and Clinical Genetics, Leiden University Medical Center (LUMC), 72, 2333 AL, Wassenaarseweg, The Netherlands.
Mech Dev. 2001 Dec;109(2):173-81. doi: 10.1016/s0925-4773(01)00563-9.
Beta-catenin has a dual role in the cell. At the membrane, it connects E-cadherin to the actin cytoskeleton, while in the nucleus, it controls gene expression in concert with Tcf-like transcription factors. Nuclear translocation of beta-catenin is induced by the Wnt signal transduction pathway. Control of this process is essential since elevated beta-catenin levels interfere with differentiation and development, and can initiate cancer in many tissues. An important role for beta-catenin during hair follicle related development and tumorigenesis has recently been established, though little is known of its endogenous expression during the development of these structures. Here, we have investigated the expression of beta-catenin in relation to markers for proliferation, differentiation and Wnt signaling during the development of three hair follicle related structures, i.e. whiskers, normal body hair and the preputial gland, and a hair follicle-derived tumor, the epidermal cyst. We observed nuclear accumulation of beta-catenin, the hallmark of Wnt signaling, in the upper matrix, the dermal papilla, the developing ringwulst of the whisker and in the tumor, though it was never in association with proliferation or terminal differentiation. Co-localization of nuclear beta-catenin with Tcf-3/4 was found only in the dermal papilla and the developing ringwulst of the whisker, but not in the upper matrix or in the tumor. These results further elucidate the role of the Wnt signal transduction pathway during hair follicle related development and tumorigenesis and illustrate the dynamic role of beta-catenin in signal transduction and cell-adhesion.
β-连环蛋白在细胞中具有双重作用。在细胞膜上,它将E-钙黏蛋白与肌动蛋白细胞骨架相连,而在细胞核中,它与Tcf样转录因子协同控制基因表达。β-连环蛋白的核转位由Wnt信号转导通路诱导。对这一过程的控制至关重要,因为β-连环蛋白水平升高会干扰细胞分化和发育,并可在许多组织中引发癌症。最近已确定β-连环蛋白在毛囊相关发育和肿瘤发生过程中起重要作用,不过对其在这些结构发育过程中的内源性表达了解甚少。在此,我们研究了β-连环蛋白在三种毛囊相关结构(即触须、正常体毛和包皮腺)以及一种毛囊源性肿瘤(表皮囊肿)发育过程中与增殖、分化和Wnt信号标记物相关的表达情况。我们观察到β-连环蛋白的核积累,这是Wnt信号的标志,出现在上基质、真皮乳头、触须发育中的环形隆起以及肿瘤中,不过它从未与增殖或终末分化相关联。仅在真皮乳头和触须发育中的环形隆起中发现核β-连环蛋白与Tcf-3/4共定位,而在上基质或肿瘤中未发现。这些结果进一步阐明了Wnt信号转导通路在毛囊相关发育和肿瘤发生过程中的作用,并说明了β-连环蛋白在信号转导和细胞黏附中的动态作用。