GENETIC CONTROL OF VULVAL CELL FATES IN C ELEGANS

这项拟议研究的长期目标是展示如何激活 受体酪氨酸激酶/RAS/MAP激酶信号通路的调控 细胞的命运。这种保守的信号通路在多种组织中使用 在整个发育过程中，细胞对此的生理反应 途径可能有很大的不同。在哺乳动物中，这一信号通路 调节成纤维细胞、神经元和 成肌细胞。在果蝇和工场中，这一信号通路发挥着中心和 在制定身体计划和控制神经元和 上皮纹形成。 关于导致激活的事件链，我们知道得很多 最后一种信号转导蛋白(MAP激酶)。然而，人们对此知之甚少 关于发生的映射激酶激活的事件。地图是如何绘制的 激酶的激活会导致细胞形状和基因表达的变化，并且 有哪些效应器分子将MAP激酶的激活与 表达新的细胞命运？ 许多组织对RTK/RAS/MAP激酶信号通路做出反应，而这 核心信号通路已被广泛研究。然而， 不同组织之间的差异决定了对 对信号转导途径知之甚少。公共RAS/映射如何 激酶信号通路产生如此不同的信号结果？一个 简单的假设是不同的组织表达不同的MAPK 底物，从而通过MAP激活这些不同的效应器 激酶的磷酸化导致不同的细胞反应。 这项拟议的研究将阐明MAPK之间的联系机制 对基因表达变化的激活，并将定义MAPK如何 信号特异性是使用一个简单的模型系统来调节的， 易于接受强大的遗传和分子遗传方法： 线虫外阴的诱导。第一个目标是 对组织特异性转录因子进行功能分析，该转录因子可能 介导反应并确定MAP激酶的特异性 发信号。第二个目标是从基因和分子水平上识别 分析外阴细胞中MAP激酶下游功能的新基因 命运决定论。第三个目标是从分子上定义反应。 使用微阵列映射激酶信号以全局识别 MAP信号转导引起的基因表达。

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.