Role of Wnt and Noggin in development and Cancer

描述（由申请人提供）： 上皮芽发育是肺、肢体、牙齿和毛发形成的第一步。为了从单层上皮形成芽，细胞必须利用它们的细胞骨架结合细胞-细胞和细胞-基质连接来重塑它们与邻近细胞的相互作用。在定义细胞形状、极性和迁移中，最重要的是肌动蛋白细胞骨架及其与E-钙粘蛋白介导的细胞-细胞连接（粘附连接）和b1整合素介导的细胞基质连接（粘着斑）的关系。这些连接是如何利用肌动蛋白丝来完成这种重塑的，这是未知的。然而，当上皮芽形成的过程误入歧途时，灾难性的结果不仅包括物理结构的畸形，还包括恶性肿瘤。小鼠将用作培养的上皮干细胞的来源，并且它们的皮肤用作模型以表征在毛囊芽发育的早期阶段Wnt和头蛋白介导的a）肌动蛋白动力学、细胞粘附和迁移以及B）基因转录的变化。长期目标是了解各种信号通路如何汇聚以调节卵泡形态发生以及失调如何导致癌症。

DESCRIPTION (provided by applicant): Epithelial bud development is the first step in the formation of lung, limb, teeth and hair. To form a bud from a single layer of epithelium, cells must utilize their cytoskeleton in conjunction with cell-cell and cell-substratum connections to remodel their interactions with neighboring cells. Of major importance in defining cell shape, polarity and migration is the actin cytoskeleton and its associations with E-cadherin-mediated cell-cell junctions (adherens junctions) and b1 integrin-mediated cell substratum junctions (focal adhesions). Precisely how these junctions utilize actin filaments to accomplish this remodeling is unknown. However, when the process of epithelial bud formation goes astray, disastrous results can include not only malformation of physical structures but also malignancies. Mice will be used as a source of cultured epithelial stem cells and their skin used as models to characterize the Wnt and noggin mediated changes in a) actin dynamics, cell adhesion and migration, and b) gene transcription, at the early stages of hair follicle bud development. The long-term goal is to understand how various signaling pathways converge to regulate follicular morphogenesis and how misregulation leads to cancer.