Role of Wnt and Noggin in development and Cancer

Wnt 和 Noggin 在发育和癌症中的作用

基本信息

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
项目类别：
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

项目摘要

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）：上皮发育是肺，肢体，牙齿和头发形成的第一步。要从单层上皮形成芽，细胞必须与细胞细胞和细胞 - 肌膜连接结合使用其细胞骨架，以重塑其与相邻细胞的相互作用。定义细胞形状，极性和迁移的主要重要性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整合蛋白介导的细胞底部连接（焦点粘附）的关联。这些结构如何利用肌动蛋白丝完成此重塑是未知的。但是，当上皮芽的过程误入歧途时，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及其皮肤用作模型，以表征Wnt和Noggin介导的变化A）肌动蛋白动力学，细胞粘附和迁移以及b）基因转录，在毛囊的早期阶段芽开发。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不调节如何导致癌症。