Gene regulatory network controlling commitment to ear identity

基因调控网络控制对耳朵身份的承诺

基本信息

批准号：
8996151
负责人：
Marianne Bronner
金额：
$ 48.35万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-12 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8996151
关键词：
Accounting Affect Algorithms Auditory Binding Bioinformatics Biology Birth Candidate Disease Gene Cell physiology Cells Child Childhood Communication Complex Congenital Abnormality DNA Sequence Alteration DNA-Protein Interaction Data Defect Development Diagnostic Ear Endolymph Enhancers Environment Equilibrium Etiology Event Fibroblast Growth Factor Future Gene Expression Gene Expression Profiling Gene Targeting Genes Genetic Genetic Counseling Goals Hair Cells Hearing Hearing Impaired Persons Individual Infection Labyrinth Lead Modeling Molecular Molecular Analysis Monitor Multipotent Stem Cells Mus Mutagenesis Newborn Infant Organism Otic Placodes Pathway interactions Pattern Pharmaceutical Preparations Phenotype Phylogenetic Analysis Pregnancy Presbycusis Prevention Process Proteins Regenerative Medicine Regulator Genes Regulatory Element Research Sampling Sense Organs Sequence Homology Signal Pathway Signal Transduction Simple Epithelium Social Interaction Speech Staging Stem Cell Research Stem cells Technology Testing Time Transcript base congenital deafness data integration deafness design differential expression ear development falls gene function genetic analysis genome sequencing hearing impairment hindbrain human disease in vivo interdisciplinary approach loss of function mathematical model nano-string new technology novel novel strategies progenitor research study response spatial integration tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): The vertebrate inner is the most complex of the sense organs responsible for hearing and balance. Yet during development it forms from a simple epithelium, the otic placode. During development of the ear, multipotent progenitor cells become progressively restricted in their potential. This process is controlled by regulatory genes whose temporal and spatial expression patterns are tightly regulated in an orchestrated gene regulatory network (GRN). We and others have established a hierarchy of events controlling the specification and determination of inner ear progenitors and identified some of the regulatory genes involved. Based on this information, we have established a preliminary network controlling these processes and designed a molecular screen to identify novel otic specifiers. We have defined co-regulated groups of genes that reflect different stages of ear specification. We will now harness genome sequence information, new technology to monitor changes in the expression of more than 100 genes simultaneously and newly developed bioinformatics tools to build up and verify the preliminary GRN. Specifically we will: " identify new genes responsive to otic inducing signals " establish the epistatic relationships between ear specific transcription factors and signaling components " isolated and characterize enhancers controlling transcription factor expression in the ear and examine direct inputs " predict common upstream regulators for genes in each synexpression group using newly developed algorithms and test the predicted regulators in vivo. This will uncover the basic GRN controlling the specification of inner ear progenitors together with its terminal target genes. In the future, this GRN will serve as a basis for studying protein-protein and protein-DNA interactions to build up a complete network, for quantitative analysis and mathematical modeling of this process, as well as a platform to discover new candidate genes for human disease affecting hearing and balance.

描述（由申请人提供）：脊椎动物内部是负责听力和平衡的感觉器官中最复杂的。然而，在开发过程中，它是由简单的上皮形成的，即耳片。在耳朵的发育过程中，多能细胞的潜力逐渐受到限制。该过程由调节基因控制，其时间和空间表达模式在精心策划的基因调节网络（GRN）中受到严格调节。我们和其他人建立了控制内耳祖细胞规范和确定的事件的层次结构，并确定了一些涉及的调节基因。基于这些信息，我们建立了一个控制这些过程的初步网络，并设计了一个分子屏幕来识别新型的耳式指示符。我们定义了反映耳朵规格不同阶段的共同调节基因组。现在，我们将利用基因组序列信息，新技术，以同时监测100多个基因表达的变化，并新开发的生物信息学工具来构建和验证初步GRN。具体而言，我们将：“确定对动态诱导信号的响应的新基因”建立了耳朵特异性转录因子和信号传导组件之间的敏科关系”隔离并表征了在耳朵中控制转录因子表达的增强子，并检查了直接输入，并检查了使用新开发的Algoriths和Test test test test test vive Socultors viv ins viv ins viv ins viv ins viv ins viv ins in synexpression conse ney synexpression for synexpression群体中的常见上游调节器。这将发现控制内耳祖细胞规范的基本GRN及其末端靶基因。将来，该GRN将作为研究蛋白质 - 蛋白质蛋白质和蛋白-DNA相互作用以建立完整网络的基础，以进行定量分析和数学建模，以及一个平台，以发现影响听力和平衡的人类疾病的新候选基因。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome.

DOI：
10.1242/dmm.019547
发表时间：
2015-09
期刊：
Disease models & mechanisms
影响因子：
4.3
作者：
Ahmed M;Ura K;Streit A
通讯作者：
Streit A

Morpholinos: studying gene function in the chick.

Morpholinos：研究小鸡的基因功能。

DOI：
10.1016/j.ymeth.2013.10.009
发表时间：
2014
期刊：
Methods (San Diego, Calif.)
影响因子：
0
作者：
Norris,Anneliese;Streit,Andrea
通讯作者：
Streit,Andrea

Neural induction by the node and placode induction by head mesoderm share an initial state resembling neural plate border and ES cells.

节点的神经诱导和头部中胚层的基板诱导共享类似于神经板边界和ES细胞的初始状态。

DOI：
10.1073/pnas.1719674115
发表时间：
2018
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Trevers KE
通讯作者：
Trevers KE

A systems-level approach reveals new gene regulatory modules in the developing ear.

DOI：
10.1242/dev.148494
发表时间：
2017-04-15
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
Chen J;Tambalo M;Barembaum M;Ranganathan R;Simões-Costa M;Bronner ME;Streit A
通讯作者：
Streit A

Directional cell movements downstream of Gbx2 and Otx2 control the assembly of sensory placodes.

Gbx2 和 Otx2 下游的定向细胞运动控制感觉基板的组装。