Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
Development. 2012 Apr;139(8):1522-33. doi: 10.1242/dev.076463.
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/β-catenin activity and regulate fibroblast cell proliferation and initiation of hair follicle placodes. In the absence of dermal Wnt signaling/β-catenin activity, patterned upregulation of epidermal β-catenin activity and Edar expression are absent. Conversely, forced activation of β-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/β-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program.
真皮成纤维细胞是皮肤结构完整性和毛囊发育所必需的。在毛囊起始前，真皮成纤维细胞前体中存在均匀的 Wnt 信号活性，但在皮肤分化和模式形成的早期阶段，真皮 Wnt 信号的功能需求在很大程度上仍未得到充分描述。我们在小鼠中表明，表皮 Wnt 配体对于均匀的真皮 Wnt 信号/β-连环蛋白活性是必需的，并调节成纤维细胞的增殖和毛囊基板的起始。在缺乏真皮 Wnt 信号/β-连环蛋白活性的情况下，表皮β-连环蛋白活性和 Edar 表达的图案上调缺失。相反，β-连环蛋白信号的强制激活导致真皮增厚、表皮基板增大和真皮凝聚物的形成，导致过早分化的增大的毛囊。这些数据揭示了真皮 Wnt 信号/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。
