Follicular Patterning Directed By Janus Kinase Signaling

Janus 激酶信号传导指导的滤泡图案形成

• 批准号: 0318776
• 负责人: Douglas Harrison
• 金额: --
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0318776&HistoricalAwards=false
• 关键词: Follicular; Patterning; Directed; Janus; Kinase

0318776HarrisonA small number of defined signaling pathways have emerged as reutilized intracellular signaling cascades that initiate cellular responses. One of these is the Janus kinase (JAK) signaling pathway. JAK signaling is the primary component of the response of many vertebrate cells to a many cytokines and growth factors. Consequently, the JAK pathway is essential for a many developmental events, including hematopoiesis, immune system development, and general growth. The pathway has been evolutionarily conserved from insects to human. Study of JAK signaling in the fruitfly, Drosophila melanogaster, is particularly attractive because it is amenable to genetic and developmental manipulation and is much simpler than the vertebrate counterpart, with only single representatives of each type of pathway molecule. As in vertebrates, the pathway is critical to many developmental events. Previously funded NSF activities have uncovered a requirement for JAK signaling in the patterning of the follicular epithelium, the monolayer of somatic cells that covers the developing egg and forms the eggshell and specialized structures. The follicular epithelium is comprised of 5 different cell fates that are determined by their position along the anterior-posterior axis The JAK ligand, Upd, as well as a homologous protein, are secreted from the poles of the egg chamber and a gradient of JAK pathway activity is created that is highest at the anterior and posterior termini. The gradient of JAK pathway activity determines the fates of the follicular cells. This suggests that Upd may act as a classical morphogen, a molecule that patterns a field of tissue into different cell fates that are assigned by virtue of position relative to the morphogen source.The two primary goals of this research will address the hypothesis that Upd may act as a morphogen. First, the mechanisms by which a gradient of JAK pathway activity is established in the follicular epithelium will be determined. The distribution of the Upd and homologous proteins their contributions to activation of the JAK pathway and establishment of epithelial pattern will be assessed. Second, the mechanisms by which the Upd ligand is transported to receiving cells will be examined. Known morphogens are distributed by passive diffusion, active endocytic transport, or a combination of the two. The contributions of these mechanisms to distribution of Upd and homologues will be examined.The proposed research will be carried out primarily as the major training activity of graduate students. Additional roles will be played by undergraduates seeking learn about biology through conducting independent research projects. As in the past, the majority of students involved in these research activities are likely to be women and/or Kentucky natives. Results of the proposed activities will be presented at professional meetings by the students who carry out the research.

已经出现了少量确定的信号传导途径作为启动细胞应答的再利用的细胞内信号传导级联。 其中之一是Janus激酶（JAK）信号通路。 JAK信号传导是许多脊椎动物细胞对许多细胞因子和生长因子的应答的主要组分。 因此，JAK通路对于许多发育事件是必不可少的，包括造血、免疫系统发育和一般生长。 从昆虫到人类，该途径在进化上是保守的。 果蝇中JAK信号的研究特别有吸引力，因为它适合遗传和发育操纵，并且比脊椎动物的对应物简单得多，每种类型的通路分子只有单一的代表。 在脊椎动物中，这条通路对许多发育事件至关重要。 以前资助的NSF活动已经揭示了JAK信号在滤泡上皮细胞模式中的需求，滤泡上皮细胞是覆盖发育中的卵子并形成蛋壳和专门结构的体细胞单层。 滤泡上皮由5种不同的细胞命运组成，这取决于它们沿前后轴的位置沿着。JAK配体Upd以及同源蛋白质从卵室的两极分泌，并且产生JAK途径活性的梯度，其在前端和后端最高。 JAK途径活性的梯度决定滤泡细胞的命运。 这表明，Upd可能作为一个经典的morphogen，一种分子，模式的组织领域到不同的细胞命运，是凭借相对于morphogen source.The两个主要目标分配的位置，这项研究将解决的假设，Upd可能作为一个morphogen。 首先，将确定在滤泡上皮中建立JAK途径活性梯度的机制。 将评估Upd和同源蛋白的分布及其对JAK途径活化和上皮模式建立的贡献。 其次，将检查Upd配体被转运到接收细胞的机制。 已知的形态发生素通过被动扩散、主动内吞转运或两者的组合分布。 这些机制对Upd和同系物分布的贡献将被检查。拟议的研究将主要作为研究生的主要培训活动进行。 通过进行独立研究项目寻求学习生物学的本科生将扮演其他角色。 和过去一样，参与这些研究活动的大部分学生可能是妇女和/或肯塔基州本地人。 拟议活动的结果将由进行研究的学生在专业会议上提出。