A Study of Biological Function of Basonuclin

我们的长期目标是了解Basonuclin基因在皮肤和头发中的作用 毛囊生物学。Basonuclin(BNC1)是一种锌指蛋白，广泛存在于 表皮和毛囊的角质形成细胞。我们认为，它协调了 其他基因则通过转录因子的活性发挥作用。我们的生化和生物信息学 研究表明，BNC1通过六种不同的途径调控基因转录。这个 BNC1调控网络与EGFR、p38 MAPK和TGFα等通路相连。 这些基因控制着重要的细胞功能，如增殖、迁移和 差异化。BNC1在基底细胞癌(BCC)中表达上调。我们对BNC1的研究 基因敲除模型表明，拔发后毛囊再生需要它， 而BNC1零突变会推迟拔发后毛囊干细胞的恢复。 在这个方案中，我们将评估BNC-1和BNC-2在皮肤中的作用 再生、伤口修复和毛囊循环。我们将描述BNC1是如何- 零突变会影响毛发再生，包括确定哪个细胞 过程受这种突变的影响以及分子扰动是由什么引起的 BNC1-零突变。通过检测BNC-1和BNC-2单基因敲除和双基因敲除小鼠，我们 将评估这些基因对维持上皮干细胞的作用 凸起以及这些细胞对损伤的反应。利用我们现有的老鼠 为了研究隆起干细胞的命运，我们将追踪运动和 BNC突变小鼠拔毛和皮肤损伤后隆起细胞的作用。 我们将利用缺失的小鼠来研究BNC与EGFR途径的相互作用 受体或表达EGFR途径抑制物的小鼠。在扩散方面的变化， 分化和迁移将在体外和体内试验中进行评估。 总体而言，我们的研究将辨别删除BNC-1和BNC-2在 皮肤上皮。BNC在EGFR途径中的作用将被识别。这个 研究将对理解干细胞生物学和BNC在创伤中的作用产生影响 治愈、毛发循环和皮肤再生。

Our long-term goal is to understand the role of the basonuclin gene in skin and hair follicle biology. Basonuclin (BNC1) is a zinc finger protein found in abundance in the keratinocytes of the epidermis and hair follicle. We believe that it coordinates activity of other genes through transcription factor activity. Our biochemical and bioinformatic studies show that BNC1 regulates transcription of genes in six different pathways. The BNC1 regulatory network is linked to pathways such as EGFR, p38 MAPK and TGFalpha. These genes control important cellular functions like proliferation, migration and differentiation. BNC1 is up-regulated in basal cell carcinoma (BCC). Our study of a Bnc1 knock out model suggests that it is required for hair follicle regeneration after hairplucking, and Bnc1-null mutation delays restoration of hair follicular stem cells after hairplucking. In this proposal, we will evaluate the role of Bnc-1 and Bnc-2 in skin regeneration, wound repair and hair follicle cycling. We will characterize how the Bnc1- null mutation affects hair regeneration, including determination of which cellular processes are affected by this mutation and what molecular perturbations are caused by Bnc1-null mutation. By examining Bnc-1 and Bnc-2 single and double knockout mice, we will assess the contribution of these genes to maintenance of epithelial stem cells in the bulge as well as the response of these cells to injury. Using mice that we have developed to study the fate of bulge stem cells, we will trace the movement and contribution of bulge cells in the Bnc mutant mice following hair plucking and skin injury. We will study the interaction of BNC with the EGFr pathway using mice with deleted receptors or mice expressing inhibitors of the EGFr pathway. Changes in proliferation, differentiation and migration will be assessed in both in vitro and in vivo assays. Overall, our research will discern the effect of deleting Bnc-1 and Bnc-2 in the cutaneous epithelium. The role of Bnc’s in the EGFr pathway will be discerned. The studies will impact on understanding stem cell biology and the role of Bnc’s in wound healing, hair cycling and skin regeneration.