Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, UK.
Cell. 2011 Feb 18;144(4):577-89. doi: 10.1016/j.cell.2011.01.014.
The hair follicle bulge in the epidermis associates with the arrector pili muscle (APM) that is responsible for piloerection ("goosebumps"). We show that stem cells in the bulge deposit nephronectin into the underlying basement membrane, thus regulating the adhesion of mesenchymal cells expressing the nephronectin receptor, α8β1 integrin, to the bulge. Nephronectin induces α8 integrin-positive mesenchymal cells to upregulate smooth muscle markers. In nephronectin knockout mice, fewer arrector pili muscles form in the skin, and they attach to the follicle above the bulge, where there is compensatory upregulation of the nephronectin family member EGFL6. Deletion of α8 integrin also abolishes selective APM anchorage to the bulge. Nephronectin is a Wnt target; epidermal β-catenin activation upregulates epidermal nephronectin and dermal α8 integrin expression. Thus, bulge stem cells, via nephronectin expression, create a smooth muscle cell niche and act as tendon cells for the APM. Our results reveal a functional role for basement membrane heterogeneity in tissue patterning. PAPERCLIP:
表皮的毛囊隆突与竖毛肌(APM)相连,竖毛肌负责毛发竖立(“鸡皮疙瘩”)。我们表明,隆突中的干细胞将肾小囊蛋白沉积到下面的基底膜中,从而调节表达肾小囊蛋白受体α8β1 整联蛋白的间质细胞与隆突的黏附。肾小囊蛋白诱导α8 整联蛋白阳性间质细胞上调平滑肌标志物。在肾小囊蛋白敲除小鼠中,皮肤中形成的竖毛肌较少,它们附着在隆突上方的毛囊上,那里的肾小囊蛋白家族成员 EGFL6 代偿性上调。α8 整联蛋白的缺失也消除了 APM 对隆突的选择性锚定。肾小囊蛋白是 Wnt 的靶标;表皮β-连环蛋白的激活上调表皮肾小囊蛋白和真皮α8 整联蛋白的表达。因此,隆突干细胞通过表达肾小囊蛋白,为 APM 创造了平滑肌细胞龛,并充当 APM 的肌腱细胞。我们的结果揭示了基底膜异质性在组织模式形成中的功能作用。