DEVELOPMENTAL REGULATION AND FUNCTION OF T1ALPHA

人们对肺泡上皮细胞的分子功能知之甚少 1型细胞或有关的监管机制，导致其 独特的建筑，即使它的形成是至关重要的， 成功的肺发育和出生后的肺修复。 这 该项目的重点是T1 α的分子调控， 我们克隆了一个啮齿类动物的基因，并对其进行了鉴定， 1型细胞，并探讨了T1 α的功能， 蛋白在发育过程中，T1 α主要表达于 脑和肺的上皮细胞;器官中的表达下调 而不是肺。 这些研究将测试 以下假设：1. T1 α的表达是 受经典的蛋白质相互作用的转录调控 在基因中具有顺式元件的转录因子， 但II型细胞不表达该蛋白。 在非表达肺中 上皮细胞如气道细胞和脑细胞T1 α可以 受启动子甲基化的调控。 2. 体外和 体内L型和II型细胞可能表达分子 表型，但不同时表达两者。 3. T1 α蛋白作为细胞功能的调节剂 与离子和水穿过或穿过类型1的运动有关 细胞基于脉络丛和睫状神经的已知功能 也表达T1 α的眼睛上皮细胞。 使用 分子、细胞和转基因方法，我们将测试这些 肺和脑细胞系中的假设，原代肺细胞中的假设，肺 和脑组织，以及完整的动物。

Very little is known about the molecular functions of the alveolar type 1 cell or about the regulatory mechanisms that lead to its distinctive architecture even though its formation is critical to successful lung development and to postnatal lung repair. This project if focused on the molecular regulation of T1 alpha, a rodent gene we cloned and characterized that is specific in lung for the type 1 cell, and explores the functions of the T1 alpha protein. During development T1 alpha is expressed mainly in epithelia of brain and lung; expression is down-regulated in organs other than lung as development proceeds. These studies will test the following hypotheses: 1. Expression of T1 alpha is transcriptionally regulated by classic interactions of protein transcription factors with cis-elements in the gene such that type l but not type ll cells express the protein. In non-expressing lung epithelial cells, such as airway cells, and brain cells T1 alpha may be regulated by methylation of the promoter. 2. In vitro and likely in vivo type l and ll cells can express the molecular phenotype of either cell but do not express both simultaneously. 3. T1 alpha protein acts as a modulator of cellular functions related to movements of ions and water across or through type 1 cells. Based on known functions of the choroid plexus and ciliary epithelium of the eye that also express T1 alpha. Using molecular, cellular, and transgenic approaches we will test these hypotheses in lung and brain cell lines, in primary lung cells, lung and brain tissues, and in intact animals.