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Mechanisms of growth control in developing Drosophila epithelia

果蝇上皮发育中的生长控制机制

基本信息

批准号：
10001356
负责人：
Kenneth H Moberg
金额：
$ 30.55万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-06 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001356
关键词：
Address Adhesives Adolescent Adult Alleles Apical Apoptosis Area Binding Biology Cadherins Cancerous Cell Nucleus Cell Proliferation Cell Survival Cells Complex Cues Data Development Disease Drosophila genus Drosophila melanogaster Ecdysone Ecdysterone Elements Elephants Embryo Enhancers Enzymes Epithelial Epithelial Attachment Epithelium Estrogens Eye Fat Body Gene Expression Genes Genetic Genetic Transcription Goals Gonadal Steroid Hormones Growth Homeostasis Hormones Human Hyperplasia Injury Knowledge Larva Lead Learning Ligand Binding Domain Ligands Light Link Malignant Neoplasms Mediating Messenger RNA Mixed Function Oxygenases Modeling Mus Natural regeneration Newborn Infant Nuclear Nutrient Occupations Organ Organ Size Organism Pathologic Pathway interactions Pattern Phenocopy Phosphorylation Physiologic pulse Physiological Porifera Privatization Process Production Protein-Serine-Threonine Kinases Proteins Role Scallop Sequence-Specific DNA Binding Protein Signal Transduction Site Source Standardization Stress Testing Testosterone Time Tissues Transcription Coactivator Transgenic Organisms Translating Vertebrates Wing Work appendage base biochemical tools blastema disc regeneration ecdysone receptor experimental study fly human disease in vivo injured morphogens programs promoter receptor regenerative sensor steroid hormone tumor wound healing

项目摘要

Project Summary/Abstract The overall goal of this proposal is to understand how organisms as diverse as humans and the fruit flies use the same molecules to determine how large their organs will grow. The specific focus of this application is a protein that promotes growth called Yorkie. In our cells it is called Yap1, however it performs the same job in both species. When Yorkie/Yap1 is `active' in cells, it tells the cells to grow and divide, and thus generates many new cells. This makes tissues larger since they have more cells, but it can also lead to the growth of a cancerous tumor. We know a bit about how Yorkie/Yap1 become `active' but not enough to reliably predict when and where this happens, or how it promotes cancer when it becomes `active' all the time. We have found another protein that physically binds to Yorkie called Taiman, and we think Taiman may be key to understanding when and where Yorkie gets activated. Taiman itself has to get `activated', but in this case we know more about this happens. Taiman gets `activated' by the fly equivalent of the human sex hormones estrogen and testosterone. We think that when these hormones `activate' Taiman that they also activate Yorkie, and that this is an important way receive signals to grow and divide. The experiments we propose will address this hypothesis in a number of ways. We will test our idea that some cells can make their own fly `sex hormone' (called ecdysone), and that how much ecdysone they make controls when and where Taiman and Yorkie get activated in adolescent flies. This kind of patterned `activation' of Yorkie/Yap1 may be part of why we grow organs & appendages in the right places each time an embryo develops into a newborn baby, and by extension how inappropriate `actvation' of Yorkie/Yap1 at the wrong place and time can drive disease. We will also test another idea that cells with `activated' Yorkie and Taiman actually think they are part of a healing wound and start the process of regeneration to fill in the missing cells and tissue. Although we use flies to study these ideas, we remain confident that much of what we learn will teach us about how all of the proteins work in our cells.

项目总结/摘要这项提案的总体目标是了解像人类和果蝇这样不同的生物是如何利用同样的分子来决定他们的器官会长多大。本申请的具体重点是一种促进生长的蛋白质叫约克。在我们的细胞中，它被称为Yap 1，但它在细胞中执行相同的工作。两个物种。当Yorkie/Yap 1在细胞中“活跃”时，它会告诉细胞生长和分裂，从而产生许多新的细胞。这使得组织更大，因为它们有更多的细胞，但它也可能导致生长的细胞。恶性肿瘤我们对Yorkie/Yap 1如何变得“活跃”有一点了解，但还不足以可靠地预测这种情况发生的时间和地点，或者当它一直变得“活跃”时，它是如何促进癌症的。我们已经发现了另一种蛋白质，物理结合约克称为泰曼，我们认为泰曼可能是这是了解约克何时何地被激活的关键泰曼本身必须得到“激活”，但在这方面，以防我们对这件事有更多了解泰曼得到'激活'的苍蝇相当于人类的性别雌激素和睾丸激素。我们认为，当这些激素'激活'泰曼，他们也激活约克，这是一个重要的方式接收信号的增长和分裂。我们提出的实验将以多种方式解决这一假设。我们将测试我们的想法，有些细胞可以制造自己的苍蝇“性激素”（称为蜕皮激素），控制何时何地泰曼和约克在青春期苍蝇中被激活。这种模式化的“激活” Yorkie/Yap 1的基因可能是为什么我们每次胚胎发育时都在正确的地方生长器官和附属物的部分原因。发展成一个新生儿，并通过扩展如何不适当的'actvation'约克/雅普1在错误的地点和时间可以驱动疾病。我们还将测试另一个想法，即细胞与'激活'约克和泰曼实际上，我认为它们是愈合伤口的一部分，并开始再生过程，以填补缺失的细胞和组织。虽然我们用苍蝇来研究这些想法，但我们仍然相信，我们学到的大部分东西将告诉我们所有的蛋白质是如何在细胞中工作的。