Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis
Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis
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DOI：
10.1101/gad.1886910
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发表时间：
2010-07-15
影响因子：
10.5
通讯作者：
Dotto, G. Paolo
中科院分区：
文献类型：
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作者：
Hu, Bing;Lefort, Karine;Dotto, G. Paolo
上皮-间充质相互作用是皮肤形态发生和体内平衡的关键。我们报道，在具有“典型”Notch信号效应的CSL/RBP-J kappa基因间充质缺失的小鼠中，毛囊角质形成细胞命运的维持存在缺陷。毛囊重建分析表明，这可以归因于真皮乳头细胞的内在缺陷。Wnt5a的缺失对毛囊分化产生了类似的影响，Wnt5a是一种特殊的真皮乳头特征基因，我们发现在这些细胞中，Wnt5a受Notch/CSL的直接控制。功能修复实验证实Wnt5a是Notch-CSL信号传导的重要下游介质，影响毛囊关键调控基因FoxN1在角质形成细胞室中的表达。由此可见，Notch/CSL信号通路以Wnt5a信号通路和FoxN1为介质，在毛囊分化调控中发挥着独特的作用。
Epithelial-mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-J kappa gene, the effector of "canonical'' Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch-CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.