Neural defects in zebrafish auditory/vestibular mutants
斑马鱼听觉/前庭突变体的神经缺陷
基本信息
- 批准号:10412441
- 负责人:
- 金额:$ 47.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcousticsAffectAfferent NeuronsAnatomyAnimalsAreaAuditoryAuditory systemBehavioralBiogenesisBiological ProcessBiologyBrainCalciumChemicalsCuesDataData SetDefectDevelopmentDiseaseDizzinessDown-RegulationENG geneEpigenetic ProcessEquilibriumEye MovementsFailureFishesFunctional disorderGene ExpressionGene Expression ProfileGene Expression RegulationGene TargetingGenerationsGenesGeneticGenetic TranscriptionGerman populationGoalsHair CellsHearingHumanImageImaging DeviceImpairmentIn Situ HybridizationLabelLabyrinthLarvaLesionLinkLocationMethodsMidbrain structureMissense MutationMolecularMolecular AnalysisMutagenesisMutationNatureNeuraxisNeurologicNeuronsNonsense MutationOpticsPatientsPeripheralPhenotypePhysiologicalPhysiologyPopulationPosturePrevalenceProteinsProxyReflex actionResearchResolutionRestSiblingsSignal TransductionStimulusSwimmingSynapsesSystemTestingTinnitusTranscriptUntranslated RNAUp-RegulationVacuolar Protein SortingVertebratesVertigoZebrafishattenuationbasebehavioral phenotypingbehavioral responsebrain morphologycell typecellular imagingclinical heterogeneityexosomeexperimental studyforward geneticsgenetic approachhearing impairmenthearing screeninghindbraininsightmaculamarker transgenesmechanotransductionmutantnovelrelating to nervous systemresponsetranscription factortranscriptome sequencingtranscriptomics
项目摘要
PROJECT SUMMARY
Approximately one quarter of patients with vertigo or dizziness have central vestibular disorders.
In addition, hearing loss or tinnitus can have central origins. Despite the prevalence of central
deficits in the auditory/vestibular system in patients, our understanding of central dysfunction at
the molecular or cellular level in vertebrates is lacking. Here, we propose to characterize a novel
class of zebrafish mutants that have central auditory/vestibular deficits to gain insights into this
understudied area of research. This proposal focuses on two mutants: raumschiff and starliner,
which were isolated from chemical mutagenesis screens for hearing and balance defects.
Unlike our previously characterized mutants, raumschiff and starliner mutants have normal
vestibular induced eye movements despite presenting with an obvious balance defect while
swimming or at rest. In addition, a defect in hearing is present in both mutants. We have
identified mutations in two genes: in starliner mutants, the split ends (spen) gene harbors a
nonsense mutation and in raumschiff we identified a missense mutation in vacuolar protein
sorting 4a (vps4a). RNAseq anaylsis of mutant and sibling transcripts indicate that both mutants
have striking misregulation of gene expression in the hindbrain and midbrain regions, yet their
development and gross brain morphology is normal. These results suggest that the defects are
functional in nature and may involve circuit level or synaptic changes. To gain a better
understanding of the central defects, we will take advantage of imaging whole fish expressing
relevant transgene markers and use newly developed methods for brain-wide imaging of cellular
responses to auditory and vestibular stimuli. These experiments will focus on the regions or cell
types where misregulation of gene expression is most prevalent. Collectively our studies will
enhance our understanding of the genes and regulatory networks involved in central function.
项目摘要
大约四分之一的眩晕或头晕患者患有中枢性前庭障碍。
此外,听力损失或耳鸣可以有中央起源。尽管中央
缺陷的听觉/前庭系统的患者,我们的理解中枢功能障碍,
在脊椎动物中缺乏分子或细胞水平。在这里,我们建议将一部小说
一类具有中枢听觉/前庭缺陷的斑马鱼突变体,
未被充分研究的领域。这个提议集中在两个突变体上:raumschiff和starliner,
其是从针对听力和平衡缺陷的化学诱变筛选中分离的。
不像我们以前描述的突变体,raumschiff和starliner突变体有正常的
尽管存在明显的平衡缺陷,但前庭诱导的眼球运动,
游泳或休息。此外,两种突变体都存在听力缺陷。我们有
在两个基因中发现了突变:在starliner突变体中,分裂末端(spen)基因携带一个
在raumschiff中,我们发现了一个空泡蛋白的错义突变,
排序4a(vps 4a)。对突变体和同胞转录物的RNAseq分析表明,两种突变体均
在后脑和中脑区域有显著的基因表达失调,
发育和大体脑形态正常。这些结果表明,
本质上是功能性的,并且可能涉及电路水平或突触变化。更好地
了解中心缺陷,我们将利用成像全鱼表达
相关的转基因标记,并使用新开发的方法进行细胞的全脑成像,
对听觉和前庭刺激的反应。这些实验将集中在区域或细胞
基因表达失调最为普遍的类型。我们的研究将
增强我们对参与中枢功能的基因和调控网络的理解。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Teresa A Nicolson其他文献
Teresa A Nicolson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Teresa A Nicolson', 18)}}的其他基金
Molecular Analysis of Tmie in sensory hair cells
感觉毛细胞中 Tmie 的分子分析
- 批准号:
10395471 - 财政年份:2018
- 资助金额:
$ 47.42万 - 项目类别:
Molecular Analysis of Tmie in sensory hair cells
感觉毛细胞中 Tmie 的分子分析
- 批准号:
9901368 - 财政年份:2018
- 资助金额:
$ 47.42万 - 项目类别:
Characterization of the Mechanotransduction complex in hair cells
毛细胞中机械转导复合物的表征
- 批准号:
9901377 - 财政年份:2015
- 资助金额:
$ 47.42万 - 项目类别:
Characterization of the mechanotransduction complex in hair cells
毛细胞中机械转导复合物的表征
- 批准号:
9246481 - 财政年份:2015
- 资助金额:
$ 47.42万 - 项目类别:
Characterization of the mechanotransduction complex in hair cells
毛细胞中机械转导复合物的表征
- 批准号:
8885946 - 财政年份:2015
- 资助金额:
$ 47.42万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
8685235 - 财政年份:2013
- 资助金额:
$ 47.42万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
8546558 - 财政年份:2013
- 资助金额:
$ 47.42万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
8874954 - 财政年份:2013
- 资助金额:
$ 47.42万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
9093769 - 财政年份:2013
- 资助金额:
$ 47.42万 - 项目类别:
Genetic and molecular dissection of hair-cell function
毛细胞功能的遗传和分子解剖
- 批准号:
7065152 - 财政年份:2004
- 资助金额:
$ 47.42万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 47.42万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 47.42万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 47.42万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 47.42万 - 项目类别:
Grant-in-Aid for Early-Career Scientists