Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation
Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation
复制标题
DOI：
10.1242/dev.076463
复制
发表时间：
2012-04-15
期刊：
影响因子：
4.6
通讯作者：
Atit, Radhika
中科院分区：
文献类型：
--
作者：
Chen, Demeng;Jarrell, Andrew;Atit, Radhika
真皮成纤维细胞是皮肤结构完整性和毛囊发育所必需的。均匀的Wnt信号传导活性存在于毛囊起始之前的真皮成纤维细胞前体中，但是在皮肤分化和图案形成的早期阶段真皮Wnt信号传导的功能需求仍然很大程度上未被表征。我们在小鼠中发现，表皮Wnt配体是均匀的真皮Wnt信号传导/β-连环蛋白活性所必需的，并调节成纤维细胞增殖和毛囊基板的启动。在缺乏真皮Wnt信号传导/β-连环蛋白活性的情况下，不存在表皮β-连环蛋白活性和Edar表达的模式上调。相反，β-连环蛋白信号传导的强制激活导致形成增厚的真皮、扩大的表皮基板和真皮冷凝物，其导致过早分化的扩大的毛囊。这些数据揭示了真皮Wnt信号传导/β-连环蛋白在成纤维细胞增殖和表皮毛囊起始程序中的功能作用。
Dermal fibroblasts are required for structural integrity of the skin and for hair follicle development. Uniform Wnt signaling activity is present in dermal fibroblast precursors preceding hair follicle initiation, but the functional requirement of dermal Wnt signaling at early stages of skin differentiation and patterning remains largely uncharacterized. We show in mice that epidermal Wnt ligands are required for uniform dermal Wnt signaling/beta-catenin activity and regulate fibroblast cell proliferation and initiation of hair follicle placodes. In the absence of dermal Wnt signaling/beta-catenin activity, patterned upregulation of epidermal beta-catenin activity and Edar expression are absent. Conversely, forced activation of beta-catenin signaling leads to the formation of thickened dermis, enlarged epidermal placodes and dermal condensates that result in prematurely differentiated enlarged hair follicles. These data reveal functional roles for dermal Wnt signaling/beta-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program.