Epithelial Cell Reintegration in Development and Disease

项目摘要 许多上皮组织是二维的细胞片。最近的工作来自多个 系统表明，错位的上皮细胞可以重新整合回床单， 表明这一过程是组织发育的共同特征。我们的目标是 理解这个过程。我们之前在果蝇Drosophila melanogaster中的工作 表明细胞重组在缺乏嗜同性粘附分子的情况下失败， 细胞间边界线。这一观察结果引发了一个问题：同样的 分子介导其他系统的重新整合。我们的初步研究还表明 这些分子与其他结构成分协调来重塑细胞 正是这一进程推动了重返社会。我们提出了三 具体目标：1）确定侧向粘连是否介导三个- 三维培养的脊椎动物组织系统。2A）查明是否重新融入社会 需要粘附分子和细胞骨架成分之间的合作。2B） 确定重组能力是否仅限于新生细胞。这项工作将 阐明细胞重新整合，上皮组织的基本特性，并有助于 解释其对组织发育和维持的重要性。

PROJECT SUMMARY Many epithelial tissues are two-dimensional sheets of cells. Recent work from multiple systems shows that a misplaced epithelial cell can reintegrate back into the sheet, and suggest that this process is a common feature of tissue development. We aim to understand this process. Our previous work in the fruit fly Drosophila melanogaster showed that cell reintegration fails in the absence of homophilic adhesion molecules that line cell-cell borders. This observation raises the question of whether the same molecules mediate reintegration in other systems. Our preliminary work also suggests that these molecules coordinate with other structural components to remodel the cell after division, and that it is this process that drives reintegration. We propose three specific aims: 1) Determine whether lateral adhesion mediates reintegration in three- dimensional cultured vertebrate tissue systems. 2A) Find out whether reintegration requires cooperation between adhesion molecules and cytoskeletal components. 2B) Establish whether reintegrative capacity is limited to newly-born cells. This work will illuminate cell reintegration, a fundamental property of epithelial tissues, and help to explain its importance to tissue development and maintenance.