Usher Syndrome (USH) genes in Drosophila tubular organ morphogenesis

果蝇管状器官形态发生中的亚瑟综合症（USH）基因

基本信息

批准号：
8110791
负责人：
SeYeon Chung
金额：
$ 7.9万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-29 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8110791
关键词：
Address Affect Animal Model Apical Area BTB/POZ Domain Biochemical Blindness Cell Polarity Clinical Confocal Microscopy Cytoplasmic Protein Cytoskeletal Modeling Defect Development Disease Drosophila genus Drosophila melanogaster Elements Embryo Epithelial Cells Epithelium Faculty Genes Genetic Goals Growth Hearing Impaired Persons Homologous Gene Human Human Development Imaging Techniques Immune Immunoelectron Microscopy Inherited Knowledge Laboratories Learning Length Life Membrane Protein Traffic Molecular Morphogenesis Morphology Myosin ATPase Organ Orthologous Gene Pathway interactions Phenotype Positioning Attribute Proteins Puberty Retinitis Pigmentosa Role Salivary Glands Scaffolding Protein Severities Symptoms System Testing Tissues Trachea Tube Tubular formation Usher Syndrome Vestibular loss Work apical membrane base congenital deafness early onset fly gain of function gain of function mutation gene function human CDH23 protein human disease insight migration mutant novel overexpression research study rib bone structure spatiotemporal transcription factor

项目摘要

DESCRIPTION (provided by applicant): Usher Syndrome (USH) is the most frequent cause of hereditary deaf-blindness in humans. Depending on the severity of clinical symptoms, USH can be divided into three clinical subtypes, with USH1 the most severe form of the disease. The gene products of nine USH disease genes have been identified so far, including five USH1 genes and three USH2 genes, which are highly conserved from flies to humans. In this study, I will focus on the embryonic salivary glands and trachea of Drosophila melanogaster because they are relatively simple tubular organs highly amenable to genetic and cellular analyses and all five of the Drosophila homologues to the USH1 genes are strongly expressed in these tissues. My preliminary studies revealed that loss and/or gain-of-function mutations in the three USH1 fly homologues including ck, Cad99C and sans that I have so far examined result in defects in salivary gland morphogenesis. I will determine the role of USH genes in tubular organ morphogenesis and characterize the interaction between the USH genes and other known genes affecting apical membrane dynamics. The long-term goal of my proposed study is to learn how the USH genes function in morphogenesis of the Drosophila salivary gland and trachea. By learning how the USH genes function at the cellular and molecular level during the formation of the relatively simple Drosophila salivary gland and trachea, I expect to gain important insight into how the USH genes function in human development and disease. PUBLIC HEALTH RELEVANCE: In the proposed studies, I will characterize the Usher Syndrome (USH) genes in Drosophila tube system. USH is the most common form of deaf-blindness in humans. By characterizing USH genes in the relatively simple, but genetically amenable organs, I expect to reveal some key aspects of USH and such knowledge can then be used to address the disease.

描述（由申请人提供）：亚瑟综合症 (USH) 是人类遗传性聋盲的最常见原因。根据临床症状的严重程度，USH 可分为三种临床亚型，其中 USH1 是最严重的疾病形式。目前已鉴定出9个USH疾病基因的基因产物，其中5个USH1基因和3个USH2基因，从果蝇到人类都高度保守。在这项研究中，我将重点关注果蝇的胚胎唾液腺和气管，因为它们是相对简单的管状器官，非常适合遗传和细胞分析，并且果蝇 USH1 基因的所有五个同源物在这些组织中强烈表达。我的初步研究表明，迄今为止我已经检查过的 ck、Cad99C 和 sans 等三种 USH1 果蝇同源物的功能丧失和/或获得功能突变会导致唾液腺形态发生缺陷。我将确定 USH 基因在管状器官形态发生中的作用，并描述 USH 基因与影响顶膜动力学的其他已知基因之间的相互作用。我提出的研究的长期目标是了解 USH 基因如何在果蝇唾液腺和气管的形态发生中发挥作用。通过了解 USH 基因在相对简单的果蝇唾液腺和气管形成过程中如何在细胞和分子水平上发挥作用，我希望能够深入了解 USH 基因如何在人类发育和疾病中发挥作用。公共健康相关性：在拟议的研究中，我将描述果蝇管系统中的亚瑟综合症 (USH) 基因。 USH 是人类最常见的聋盲症。通过表征相对简单但遗传上适用的器官中的 USH 基因，我希望揭示 USH 的一些关键方面，然后可以使用这些知识来解决该疾病。