Role of Wnt and Noggin in development and Cancer

Wnt 和 Noggin 在发育和癌症中的作用

• 批准号: 6773264
• 负责人: William E Lowry
• 金额: $ 4.73万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773264
• 关键词: actins; cadherins; cell adhesion; cell migration; developmental genetics; epithelium; genetic transcription; genetically modified animals; hair follicle; histogenesis; laboratory mouse; microarray technology; postdoctoral investigator; skin; stem cells; tissue /cell culture; transcription factor; video microscopy

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.

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以及细胞与细胞和细胞与基质的连接来重塑它们与邻近细胞的相互作用。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(粘连连接)和b1整合素介导的细胞基质连接(焦点粘连)的关系是确定细胞形状、极性和迁移的重要因素。这些连接是如何利用肌动蛋白细丝来完成这种重塑的确切原因尚不清楚。然而，当上皮芽的形成过程走入歧途时，灾难性的后果不仅可能包括身体结构的畸形，还可能包括恶性肿瘤。小鼠将被用作培养上皮干细胞的来源，并将其皮肤作为模型，以表征Wnt和noggin在毛囊芽发育早期a)肌动蛋白动态、细胞黏附和迁移以及b)基因转录的变化。长期目标是了解不同的信号通路如何汇聚来调节卵泡的形态发生，以及调控不当如何导致癌症。