GENETIC CONTROL OF VULVAL CELL FATES IN C ELEGANS

拟议研究的长期目标是显示激活是如何 受体酪氨酸激酶/Ras/MAP激酶信号通路调节 细胞命运这种保守的信号通路在多种组织中使用 但细胞对此的生理反应 路径可能会有很大的不同。在哺乳动物中， 调节成纤维细胞、神经元的生长和分化， 成肌细胞在果蝇和果蝇中，这种信号通路起着中心作用， 在建立身体计划和控制神经元和 上皮图案形成。 关于导致激活的一系列事件， 最后信号转导蛋白（MAP激酶）。然而， 关于MAP激酶激活的事件。MAP如何 激酶活化导致细胞形状和基因表达变化， 什么是将MAP激酶激活与 表达新的细胞命运 许多组织都会对RTK/Ras/MAP激酶信号通路产生反应，而这 核心信号通路已被深入研究。但 每个组织中的差异，定义了对 对信号通路的了解很少。一个普通的Ras/MAP 激酶信号通路产生如此多样的信号结果？一 简单假设是不同组织表达不同的MAP激酶 底物，使得MAP激活这些不同的效应物 激酶磷酸化导致不同的细胞反应。 这项研究将阐明MAP激酶与 激活基因表达的变化，并将确定如何MAP激酶 使用简单的模型系统调节信号传导特异性， 易于适用于强大的遗传和分子遗传方法： 诱导C.优雅第一个目标是 功能性分析组织特异性转录因子，所述转录因子可以 介导反应并确定对MAP激酶的特异性 发信号。第二个目标是从基因上识别和分子上 分析外阴细胞中MAP激酶下游功能的新基因 命运决定第三个目标是从分子上定义反应 MAP激酶信号传导，以全面识别 MAP激酶信号传导引起的基因表达。

The long-term objective of the proposed research is to show how activation of the receptor tyrosine kinase/Ras/MAP kinase signaling pathway regulates cell fates. This conserved signaling pathway is used in multiple tissues throughout development, but the cell physiological response to this pathway can be dramatically different. In mammals, this signaling pathway regulates growth and differentiation of fibroblasts, neurons and myoblasts. In flies and works, this signaling pathway plays a central and crucial role in establishing the body plan and controlling neuronal and epithelial pattern formation. Much is known about the chain of events leading to the activation of the last signal transduction protein (MAP kinase). However, little is known about the events that occur that MAP kinase activation. How does MAP kinase activation lead to changes in cell shape and gene expression, and what are the effector molecules that link MAP kinase activation to the expression of new cell fates? Many tissues respond to the RTK/Ras/MAP kinase signaling pathway, and this core signaling pathway has been intensively studied. However, the differences in each tissue that define the specificity of the response to the signaling pathway are poorly understood. How can a common Ras/MAP kinase signaling pathway generate such diverse signaling outcomes? A simple hypothesis is that different tissues express different MAP kinase substrates, such that activation of these different effectors by MAP kinase phosphorylation leads to different cellular responses. The proposed research will elucidate the mechanisms linking MAP kinase activation to changes in gene expression and will define how MAP kinase signaling specificity is regulated using a simple model system that is readily amenable to powerful genetic and molecular genetic approaches: induction of the vulva in the nematode C. elegans. The first goal is to functionally analyze a tissue specific transcription factor that may mediate the response and determine the specificity to MAP kinase signaling. The second goal is to genetically identify and molecularly analyze new genes that function downstream of MAP kinase in vulval cell fate determination. The third goal is to molecularly define the response to MAP kinase signaling using microarrays to globally identify changes in gene expression caused by MAP kinase signaling.