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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=660975
• 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片的细胞组成，并且这种组织是通过组成细胞之间的物理相互作用来维持的。 我的研究项目侧重于了解上皮组织的发育，特别是相邻细胞之间相互作用的调节如何驱动表征组织发育的上皮组织和功能的变化。***以果蝇卵巢的滤泡上皮为模型，这项工作研究了决定组织特性的细胞间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方式 导致其形式和功能发生重大变化。 这项工作的一个焦点是同质细胞粘附分子 Echinoid (Ed)，我们之前证明它在上皮的形态发生中发挥着重要作用。 Ed 在该组织中显示出时间和空间动态表达模式，在这里我们建议识别 Ed 表达的上游调节因子。我们还注意到，Ed 的这种损失与发育中的卵母细胞对卵黄的摄取同时发生，这一过程涉及卵黄蛋白从循环血淋巴穿过滤泡上皮的过程。 在许多昆虫中，这种运动涉及卵泡细胞之间短暂出现的细胞间隙，允许卵黄蛋白通过。我们有兴趣了解该系统中卵黄通道的等效机制，并询问它是否需要 Ed 的损失。***目标 1：确定卵子发生过程中 Ed 表达的调节水平。 ***目标 2：测试卵子发生中期期间 Ed 表达丢失的候选上游调节因子。 ***目标 3：表征卵子发生中期卵黄穿过滤泡上皮的过程，并检验这一过程中涉及 Ed 丢失的假设。 ***长期目标：a) 应用目标 1 和 2 的方法和见解来研究胚胎中 Ed 的调节，b) 确定在卵子发生中期卵黄蛋白通过滤泡上皮的过程中涉及的其他因素。 ***结果：这项工作很重要，因为它使用特征明确的模型系统和各种体内遗传操作工具来研究细胞间相互作用的调节如何调节发育上重要的上皮特性。 它将有助于我们理解 Ed（众所周知，Ed 可以介导细胞间相互作用），并有助于解决重要分子穿过上皮屏障的调节机制的基本问题。 这项工作将为受训者提供分子生物学、组织学和先进成像技术方面的直接技术专业知识，以及沟通和批判性思维技能，为他们的各种职业道路做好准备，从而为 HQP 培训做出贡献。********