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.
项目总结
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)
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Teresa A Nicolson其他文献
Teresa A Nicolson的其他文献
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{{ 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:
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:
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:
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:
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