DEVELOPMENTAL REGULATION AND FUNCTION OF T1ALPHA

人们对肺泡的分子功能知之甚少 类型1细胞或关于导致其 独特的建筑，尽管它的形成对 成功的肺发育和出生后的肺修复。这 该项目如果专注于T1α的分子调控，a 我们克隆并鉴定了在肺中特异的啮齿动物基因 ，并探索了T1α的功能 蛋白。在发育过程中，T1α主要表达于 脑和肺上皮细胞；在器官中表达下调 而不是肺脏，随着发育的进行。这些研究将检验 假设：1.T1α的表达式为 受蛋白质经典相互作用的转录调控 转录因子中含有顺式元件的基因如L 但不是11型细胞表达这种蛋白质。在不表达的肺中 上皮细胞，如呼吸道细胞，和脑细胞T1α可以 受启动子甲基化的调控。2.体外培养和 可能在活体类型的L和LL细胞中可以表达该分子 任何一种细胞的表型，但不能同时表达两种细胞。 3.T1α蛋白是细胞功能的调节器 与离子和水穿过或通过类型1的移动有关 细胞。基于脉络丛和睫状神经的已知功能 眼上皮细胞也表达T1α。vbl.使用 我们将测试分子、细胞和转基因方法 肺和脑细胞系、原代肺细胞、肺中的假说 和脑组织，以及完好无损的动物体内。

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.