Follicular Patterning Directed By Janus Kinase Signaling

0318776 Harrison随着重新利用启动细胞反应的细胞内信号级联，出现了少量已定义的信号通路。其中之一是Janus Kinase(JAK)信号通路。JAK信号是许多脊椎动物细胞对多种细胞因子和生长因子做出反应的主要组成部分。因此，JAK通路在许多发育事件中都是必不可少的，包括造血、免疫系统发育和一般生长。从昆虫到人类，这条途径在进化上是保守的。果蝇中JAK信号的研究特别吸引人，因为它易于遗传和发育操作，而且比脊椎动物简单得多，每种途径分子只有一个代表。与脊椎动物一样，该途径对许多发育事件至关重要。以前资助的NSF活动发现，在卵泡上皮的图案中需要JAK信号，滤泡上皮是覆盖着发育中的卵子并形成蛋壳和特化结构的体细胞的单层。卵泡上皮由5个不同的细胞组成，它们的位置决定了它们在前后轴上的位置。JAK配体UPD和一个同源蛋白从卵室的两极分泌，JAK途径的活性梯度在前后端最高。JAK途径活性的梯度决定了滤泡细胞的命运。这表明UPD可能是一种经典的形态生成物，一种分子，它将组织区域划分为不同的细胞命运，这些命运是根据相对于形态来源的位置来分配的。本研究的两个主要目标将解决UPD可能作为形态生成物的假说。首先，将确定在卵泡上皮中建立JAK途径活性梯度的机制。将评估UPD和同源蛋白的分布及其在JAK途径激活和上皮模式建立中的作用。其次，将研究UPD配体被运送到接收细胞的机制。已知的形态原通过被动扩散、主动内吞运输或两者的组合来分布。将考察这些机制对UPD和同源物分布的贡献。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了解生物学的本科生将扮演额外的角色。与过去一样，参与这些研究活动的大多数学生可能是女性和/或肯塔基州原住民。建议活动的结果将由进行研究的学生在专业会议上公布。

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.