人体绝大多数器官都含有内皮或上皮类型的管状组织用以运输液体和气体。管腔形成是组织器官发育中最常见、最基础的形态发生过程之一。尽管动物和体外细胞的研究已对管腔形成的机制提供了一定的了解，但许多重要问题还没有解决。本项目将以果蝇卵巢的边界细胞簇为模型，结合遗传学、细胞生物学、活体成像、生化等方法手段，来回答以下几个科学问题：1. 转录因子dHR3如何通过协同调控顶端极性分子的分布、囊泡融合和极性运输、actin和微管细胞骨架的极性分布、磷脂和细胞膜的合成来建立新的顶基端极性并促进de novo管腔形成。2. 在不同的发育系统里dHR3是否都是de novo管腔形成过程所必需的。3. dHR3对de novo管腔形成是否具有充分性。预期结果将会提示我们在发育过程中是否存在一些普遍和保守的“主开关”来开启管腔形成。这些主开关分子的发现也将对组织和器官的再生提供应用价值。

Most of our organs require tubes of epithelial or endothelial nature to transport liquid or gas. Lumen formation is one of the most common and fundamental morphogenetic processes in development. Although animal models and cell culture studies provide some mechanistic understanding in lumen formation, many important questions have not been addressed. The proposed study plan to employ border cell model of Drosophila ovary to address the following questions. 1. How the transcription factor dHR3 coordinately regulates the distribution of apical polarity protein, polarized distribution of actin and microtubule cytoskeleton, vesicle fusion and polarized transport, and lipid and membrane biosynthesis to induce lumen formation. 2. Is dHR3 required in formation of different lumen and tubes? 3. Is dHR3 sufficient for de novo lumen formation? Expected results will allow us to better understand whether there exists “master switches” for de novo lumen formation. The discovery of such master switches will have application for tissue and organ regeneration.