Molecular Genetics of Otolith Formation in the Zebrafish

斑马鱼耳石形成的分子遗传学

基本信息

项目摘要

DESCRIPTION (provided by applicant): The general goal of this proposal is to elucidate the molecular mechanisms that govern the formation of otoliths and otoconia, the biominerals in vertebrate inner ears that convey linear accelerations to the sensory hair cells. The proteins of otoliths and otoconia are thought to play a critical role in their formation. However, testing of this hypothesis is hampered by the fact that most of these proteins are not known. The specific aims of this proposal are, therefore, first to determine the sequence of the about two dozen constituent proteins of zebrafish otoliths; second, to examine the proteins' expression patterns; and third, to test whether these proteins are necessary for otolith formation. In humans, otoconial defects are associated with common vestibular deficits, such as benign paroxysmal positional vertigo and possibly Pendred syndrome. The inaccessibility of the human labyrinth, however, calls for an animal model to study the physiology and pathology of otoconia. Zebrafish otoliths are evolutionary orthologs of mammalian otoconia, based on their shared location, function, composition, and general structure, and thus a valid model system. Furthermore, the mechanisms that govern otolith and otoconia formation are likely to be similar, based on the high degree of molecular conservation found between inner-ear structures of zebrafish and mammals. The zebrafish offers numerous experimental advantages for studies of otolith formation, such as simple husbandry, easy observation and manipulation of gene expression, a genomics infrastructure rivaling that of the mouse, and the accessibility of its transparent and externally-developing embryos. The combination of protein purification and sequencing by mass-spectrometry, molecular cloning of cDNAs, in situ hybridization and quantitative RT-PCR, morpholino injections and mutant rescue will lead to an efficient identification of candidate genes and mechanisms for future studies of mammalian otoconia.
描述(由申请人提供):本提案的总体目标是阐明控制耳石和耳石形成的分子机制,耳石和耳石是脊椎动物内耳中的生物矿物质,将线性加速度传递给感觉毛细胞。耳石和耳石的蛋白质被认为在它们的形成中起着关键作用。然而,这一假设的检验受到了大多数蛋白质未知的事实的阻碍。因此,这项建议的具体目标是,首先确定斑马鱼耳石的大约24种组成蛋白质的序列;其次,检查蛋白质的表达模式;第三,测试这些蛋白质是否是耳石形成所必需的。在人类中,耳锥缺陷与常见的前庭缺陷相关,如良性阵发性位置性眩晕和可能的Pendred综合征。然而,人类迷路的不可接近性要求动物模型来研究耳石症的生理和病理。斑马鱼耳石是哺乳动物耳石的进化直向同源物,基于它们共同的位置、功能、组成和一般结构,因此是有效的模型系统。此外,基于在斑马鱼和哺乳动物的内耳结构之间发现的高度分子保守性,控制耳石和耳石形成的机制可能是相似的。斑马鱼为耳石形成的研究提供了许多实验优势,例如简单的饲养,易于观察和操纵基因表达,可与小鼠相媲美的基因组学基础设施,以及透明和外部发育的胚胎的可及性。蛋白质纯化和质谱测序、cDNA分子克隆、原位杂交和定量RT-PCR、吗啉注射和突变体拯救的结合将为哺乳动物耳石症的进一步研究提供有效的候选基因和机制。

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 }}

Richard Kollmar其他文献

Richard Kollmar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('Richard Kollmar', 18)}}的其他基金

Restoration of Recurrent-Laryngeal-Nerve Function after Injury in a Rat Model
大鼠模型损伤后喉返神经功能的恢复
  • 批准号:
    8960931
  • 财政年份:
    2014
  • 资助金额:
    $ 28.8万
  • 项目类别:
Molecular Genetics of Otolith Formation in the Zebrafish
斑马鱼耳石形成的分子遗传学
  • 批准号:
    7961945
  • 财政年份:
    2005
  • 资助金额:
    $ 28.8万
  • 项目类别:
Molecular Genetics of Otolith Formation in the Zebrafish
斑马鱼耳石形成的分子遗传学
  • 批准号:
    6967000
  • 财政年份:
    2005
  • 资助金额:
    $ 28.8万
  • 项目类别:
Molecular Genetics of Otolith Formation in the Zebrafish
斑马鱼耳石形成的分子遗传学
  • 批准号:
    7231373
  • 财政年份:
    2005
  • 资助金额:
    $ 28.8万
  • 项目类别:
Molecular Genetics of Otolith Formation in the Zebrafish
斑马鱼耳石形成的分子遗传学
  • 批准号:
    7435339
  • 财政年份:
    2005
  • 资助金额:
    $ 28.8万
  • 项目类别:

相似海外基金

Phylogenomics and the Developmental Genetics and Evolution of Butterfly Colour Patterns
系统基因组学和蝴蝶颜色模式的发育遗传学和进化
  • 批准号:
    RGPIN-2022-05016
  • 财政年份:
    2022
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
Muscle Activity and Growth: from Developmental Genetics to the Human Population
肌肉活动和生长:从发育遗传学到人类
  • 批准号:
    MR/W001381/1
  • 财政年份:
    2022
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Research Grant
Developmental Genetics and Evolution of Butterfly Colour Patterns
蝴蝶颜色图案的发育遗传学和进化
  • 批准号:
    RGPIN-2016-06012
  • 财政年份:
    2021
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
The Developmental Genetics of Brain-Body Allometry
脑体异速发育遗传学
  • 批准号:
    RGPIN-2017-04851
  • 财政年份:
    2021
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
RUI: Unraveling the Developmental Genetics that Underlie Anuran Limb Initiation
RUI:揭示阿努拉肢体启动背后的发育遗传学
  • 批准号:
    2042146
  • 财政年份:
    2021
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Standard Grant
The Developmental Genetics of Brain-Body Allometry
脑体异速发育遗传学
  • 批准号:
    RGPIN-2017-04851
  • 财政年份:
    2020
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
Developmental Genetics and Evolution of Butterfly Colour Patterns
蝴蝶颜色图案的发育遗传学和进化
  • 批准号:
    RGPIN-2016-06012
  • 财政年份:
    2020
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
Developmental Genetics and Evolution of Butterfly Colour Patterns
蝴蝶颜色图案的发育遗传学和进化
  • 批准号:
    RGPIN-2016-06012
  • 财政年份:
    2019
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
NSF-BSF: Collaborative Research: Developmental genetics of host invasion initiated by fungal spores
NSF-BSF:合作研究:真菌孢子引发宿主入侵的发育遗传学
  • 批准号:
    1916137
  • 财政年份:
    2019
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Standard Grant
The Developmental Genetics of Brain-Body Allometry
脑体异速发育遗传学
  • 批准号:
    RGPIN-2017-04851
  • 财政年份:
    2019
  • 资助金额:
    $ 28.8万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了