Signaling Hierarchies in Vertebrate Development

脊椎动物发育中的信号传导层次

基本信息

批准号：
8051040
负责人：
CHARLES B KIMMEL
金额：
$ 4.75万
依托单位：
UNIVERSITY OF OREGON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2010-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8051040
关键词：
Address Affect American Animal Model Back Behavior Blindness Bone Development Cartilage Cells Cephalic Child Cleft Palate Complex Congenital Abnormality Core Facility Degenerative polyarthritis Development Developmental Biology Disease Embryo Enteric Nervous System Epithelium Failure Figs - dietary Gastrointestinal tract structure Gene Expression Gene Mutation Genes Genetic Genetic Screening Goals Hearing Impaired Persons Human Individual Inflammatory Bowel Diseases Investigation Laboratories Laboratory Organism Learning Life Ligands Link Logic Mediating Mesenchyme Molecular Morphogenesis Motivation Nature Neurons Oregon Organism Pathway interactions Pattern Population Proteins Recording of previous events Research Sensory Shapes Signal Pathway Signal Transduction Signaling Molecule Skeleton Specific qualifier value Structure Synapses System Testing Universities Usher Syndrome Work Zebrafish base blastomere structure bone cell type combinatorial computerized data processing developmental genetics gain of function gastrointestinal epithelium genetic analysis gut microbiota human disease improved intercellular communication notch protein novel progenitor programs receptor research study response skeletogenesis synaptogenesis

项目摘要

For all children to have the opportunity to achieve their full potential for healthy lives, free from disease, it is essential to understand mechanisms underlying developmental patterning and how this patterning can go awry in human disease. The goal of this Program Project is to elucidate one such mechanism - the function of reciprocal intercellular signaling that specifies embryonic cells to traverse particular developmental pathways and express restricted fates. This goal will be achieved for three sets of cell fates in three Component Projects (CPs), using the zebrafish, a widely-utilized animal model organism pioneered by this group at the University of Oregon. The projects take advantage of the attributes of the zebrafish for developmental genetic analyses, including gene expression analyses, genetic mosaic analyses, and loss and gain-of-function experiments that will establish the nature of the interactions. The projects include screens for new mutations and genes important in these signaling pathways, facilitated by the unique Zebrafish Facility, one of five Core Facilities. CP I "Reciprocal signaling in skeletogenesis" tests hypotheses about the functioning of signaling molecules in patterning the shape of the palatal skeleton and the pathway of chondral bone development. Results will improve understanding of signaling pathways between cranial epithelia and mesenchyme, and between cartilage and bone progenitors. They will thereby inform our understanding of cleft palate, one of the most common human birth defects, and osteoarthritis that will affect nearly one in five Americans during the coming decade. CP II "Reciprocal signaling in synaptogenesis" tests a novel hypothesis that Usher genes encode proteins that interact in a complex mediating reciprocal signaling between sensory cells and neurons with which the sensory cells form synaptic connections. The analyses will identify the critical components of the Usher gene network and provide an integrated understanding of Usher syndrome, the most frequent cause of deaf blindness. CP III "Reciprocal signaling in gastrointestinal tract development" explores the hypothesis that gut microbiota influence cell fate decisions in gut epithelium and enteric nervous system by modulating a highly conserved molecular signal, Notch. The work will elucidate reciprocal signaling and how it goes awry in disorders such as inflammatory bowel disease and related disorders that together affect more than 10% of the US population.

为了让所有儿童都有机会充分发挥健康生活的潜力，远离疾病，有必要了解发育模式的潜在机制以及这种模式如何在人类疾病中出错。该计划项目的目标是阐明一种这样的机制——指定胚胎细胞经历特定发育过程的相互细胞间信号传导的功能。途径并表达受限的命运。这一目标将通过三个组件项目（CP）中的三组细胞命运来实现，使用斑马鱼，这是俄勒冈大学该小组首创的一种广泛使用的动物模型生物。这些项目利用斑马鱼的属性进行发育遗传分析，包括基因表达分析、遗传镶嵌分析以及功能丧失和获得的实验，这些实验将确定相互作用的性质。这些项目包括在五个核心设施之一的独特斑马鱼设施的推动下，筛选这些信号通路中重要的新突变和基因。 CP I“骨骼发生中的相互信号”测试了关于信号分子在形成腭骨骼形状和软骨骨发育途径中的功能的假设。结果将增进对颅上皮和间质之间以及软骨和骨祖细胞之间信号通路的理解。因此，它们将帮助我们了解腭裂（最常见的人类出生缺陷之一）和骨关节炎，骨关节炎将在未来十年影响近五分之一的美国人。 CP II“突触发生中的相互信号”测试了一个新的假设，即 Usher 基因编码的蛋白质在介导感觉细胞和神经元之间复杂的相互信号中相互作用，感觉细胞与神经元形成突触连接。这些分析将确定 Usher 基因网络的关键组成部分，并提供对 Usher 综合征（导致聋盲的最常见原因）的综合理解。 CP III“胃肠道发育中的相互信号”探讨了肠道微生物群通过调节高度保守的分子信号 Notch 影响肠道上皮和肠神经系统中细胞命运决定的假设。这项工作将阐明相互信号传导及其在炎症性肠病和相关疾病等疾病中如何出错，这些疾病共同影响了超过 10% 的美国人口。