Regulation of cell-cell recognition during epithelial development

上皮发育过程中细胞间识别的调节

• 批准号: RGPIN-2015-06401
• 负责人: Nilson, Laura
• 金额: $ 2.19万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614128
• 关键词: Regulation; cell; recognition; during; epithelial

Epithelial tissues are composed of cells that are organized into continuous sheets, and this organization is maintained by physical interactions between the component cells. My research program focuses on understanding the development of epithelial tissues, in particular how the regulation of the interactions between neighboring cells can drive the changes in epithelial organization and function that characterize the development of the tissue. Using the follicular epithelium of the Drosophila ovary as a model, this work investigates the molecular basis for the cell-cell interactions that determine the properties of the tissue and asks how their regulation during the development of the tissue leads to important changes in its form and function. One focus of this work is the homophilic cell adhesion molecule Echinoid (Ed), which we showed previously plays an important role in morphogenesis of this epithelium. Ed displays a temporally and spatially dynamic expression pattern in this tissue, and here we propose to identify the upstream regulators of Ed expression. We also noted that this loss of Ed coincides with the uptake of yolk in the developing oocyte, a process that involves transit of yolk proteins from the circulating hemolymph across the follicular epithelium. In many insects, this movement involves the transient appearance of intercellular spaces between follicle cells that allow the passage of yolk proteins. We are interested in understanding the equivalent mechanism for yolk passage in this system, and asking whether it requires loss of Ed. Aim 1: To determine at what level Ed expression is regulated during oogenesis. Aim 2: To test candidate upstream regulators of the loss of Ed expression during mid-oogenesis. Aim 3: To characterize the passage of yolk across the follicular epithelium during mid-oogenesis and test the hypothesis that loss of Ed is involved in this process. Long term goals: a) to apply the approaches and insights from Aims 1 and 2 to investigate regulation of Ed in the embryo, and b) to identify additional factors involved in passage of yolk proteins through the follicular epithelium in mid-oogenesis. Outcomes: This work is important because it investigates, using a well-characterized model system with a variety of tools for in vivo genetic manipulation, how the modulation of cell-cell interactions regulates developmentally important epithelial properties. It will contribute to our understanding of Ed, which is known to mediate intercellular interactions, and to the fundamental question of the regulatory mechanisms that allow transit of important molecules across epithelial barriers. This work will contribute to HQP training by providing trainees with direct technical expertise in molecular biology, histology and advanced imaging techniques, and also with the communication and critical thinking skills that will prepare them for a variety of career paths.

上皮组织由组织成连续薄片的细胞组成，并且这种组织通过组成细胞之间的物理相互作用来维持。我的研究计划侧重于了解上皮组织的发展，特别是如何调节相邻细胞之间的相互作用可以驱动上皮组织和功能的变化，表征组织的发展。 以果蝇卵巢的滤泡上皮为模型，研究了决定组织性质的细胞-细胞相互作用的分子基础，并询问它们在组织发育过程中的调节如何导致其形式和功能的重要变化。这项工作的一个重点是嗜同性细胞粘附分子棘（艾德），我们以前显示起着重要的作用，这种上皮的形态发生。艾德在该组织中显示时间和空间动态表达模式，在这里，我们建议确定艾德表达的上游调控因子。我们还注意到，这种艾德的丧失与发育中的卵母细胞对卵黄的摄取相一致，这一过程涉及卵黄蛋白从循环血淋巴穿过滤泡上皮的转运。在许多昆虫中，这种运动涉及滤泡细胞之间短暂出现的细胞间隙，允许卵黄蛋白通过。我们感兴趣的是了解在这个系统中的卵黄通道的等效机制，并询问它是否需要失去ED。 目的1：确定卵子发生过程中艾德的表达水平。 目的2：检测卵子发生中期艾德表达缺失的上游调控因子。 目标三：描述卵子发生中期卵黄穿过卵泡上皮的过程，并检验艾德丢失参与这一过程的假设。 长期目标：a）应用目标1和2中的方法和见解来研究胚胎中艾德的调节，以及B）确定参与卵子发生中期卵黄蛋白通过滤泡上皮的其他因素。 成果：这项工作是重要的，因为它调查，使用一个良好的特征模型系统与各种工具在体内遗传操作，细胞-细胞相互作用的调制如何调节发育重要的上皮特性。这将有助于我们了解艾德，这是已知的介导细胞间的相互作用，并允许重要分子的转运上皮屏障的调节机制的基本问题。这项工作将有助于HQP培训，为学员提供分子生物学，组织学和先进成像技术方面的直接技术专长，以及沟通和批判性思维技能，使他们为各种职业道路做好准备。