Molecular Genetic Mechanisms of Gonad Development in Zebrafish

斑马鱼性腺发育的分子遗传机制

基本信息

  • 批准号:
    9728587
  • 负责人:
  • 金额:
    $ 36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-03-01 至 2001-02-28
  • 项目状态:
    已结题

项目摘要

The long-term objective of this project is to understand the genetic mechanisms that control gonad development in animals with backbones. The general morphology and endocrinology of gonad development are well conserved among vertebrates, but the genetic pathway that determines whether a gonad becomes an ovary or a testis is not well understood in any vertebrate. Understanding the mechanisms that regulate gonad growth and differentiation takes on increasing significance as environmental pollutants, such as some polychlorinated biphenyls (PCBs), may disturb gonad development and endocrine function in fish, birds, and mammals, including humans. The resulting effects on the physiology of reproduction are significant for the preservation of wildlife populations and for human reproductive health. Although the underlying pathway of gonad development may be shared among vertebrates, different vertebrate lineages have different ways of diverting the pathway towards an ovary or a testis. Some species have strong genotypic sex determination, such as mammals in which a specific gene called SRY on the Y-chromosome specifies gonad development. Other species have strong environmental sex determination, such as some turtles in which the temperature of embryo incubation regulates gonad sex. Investigations on zebrafish suggest the hypothesis that multiple genotypic factors, with a minor influence from the environment, cause an individual's gonads to express either genes for androgen synthesizing enzymes and androgen receptor, or express genes for estrogen synthesizing enzymes and estrogen receptor; these endocrine factors may then control the sex of the gonad, primary germ cells, and secondary sex characteristics. This hypothesis will be tested in three ways: Specific Aim 1. The proposed experiments will investigate the expression patterns of genes predicted by the model to play a role in early gonadal development of the zebrafish. Specific Aim 2: The proposed experiments will perturb gonad development using sex steroids and their inhibitors, and various mutations, and investigate whether gene expression patterns change in ways predicted by the model. Specific Aim 3: The proposed experiments will identify quantitative trait loci (QTLs) associated with sex differentiation in zebrafish. Map locations will be compared to those of genes isolated in Specific Aim 1 and with mammalian genomes to suggest candidate genes for gonad differentiation in zebrafish. Achieving the specific aims will result in a more robust understanding of the control mechanisms of gonad development in zebrafish, and will point to genetic loci that influence sex determination in this species. The resulting firmer understanding of the basic nature of sex determination in zebrafish will permit the future design of mutagenesis protocols to isolate novel genes important for vertebrate sex determination.
这个项目的长期目标是了解控制脊椎动物性腺发育的遗传机制。生殖腺发育的一般形态学和内分泌学在脊椎动物中是很保守的,但是决定生殖腺是变成卵巢还是睾丸的遗传途径在任何脊椎动物中都没有很好的理解。了解调节性腺生长和分化的机制具有越来越重要的意义,因为环境污染物,如一些多氯联苯(PCB),可能会干扰鱼类,鸟类和哺乳动物(包括人类)的性腺发育和内分泌功能。由此产生的对生殖生理的影响对野生动物种群的保护和人类生殖健康具有重要意义。 虽然性腺发育的潜在途径可能在脊椎动物中共享,但不同的脊椎动物谱系具有不同的将途径转向卵巢或睾丸的方式。有些物种有很强的基因型性别决定,如哺乳动物,其中一个特定的基因称为SRY的Y染色体指定性腺发育。其他物种有很强的环境性别决定,如一些海龟胚胎孵化的温度调节性腺性别。对斑马鱼的研究提出了一种假说,即多种基因型因素,加上环境的微小影响,导致个体的性腺表达雄激素合成酶和雄激素受体的基因,或表达雌激素合成酶和雌激素受体的基因;这些内分泌因素可能控制性腺、初级生殖细胞和第二性征的性别。 这一假设将通过三种方式进行检验:具体目标1。拟议的实验将调查模型预测的基因的表达模式,在斑马鱼的早期性腺发育中发挥作用。具体目标二:拟议的实验将使用性类固醇及其抑制剂和各种突变来干扰性腺发育,并研究基因表达模式是否以模型预测的方式变化。具体目标3:拟进行的实验将确定与斑马鱼性别分化相关的数量性状基因座(QTL)。地图的位置将进行比较,在特定目标1和哺乳动物基因组中分离的基因,以建议候选基因在斑马鱼性腺分化。 实现特定的目标将导致更强大的了解斑马鱼性腺发育的控制机制,并将指向影响该物种性别决定的遗传位点。由此产生的更坚定的理解性别决定的基本性质,在斑马鱼将允许未来设计的诱变方案,以分离新的基因重要的脊椎动物性别决定。

项目成果

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John Postlethwait其他文献

The genome of the arapaima (Arapaima gigas) provides insights into gigantism, fast growth and chromosomal sex determination system
巨骨舌鱼(Arapaima gigas)的基因组为巨大体型、快速生长和染色体性别决定系统提供了见解。
  • DOI:
    10.1038/s41598-019-41457-x
  • 发表时间:
    2019-03-28
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Kang Du;Sven Wuertz;Mateus Adolfi;Susanne Kneitz;Matthias Stöck;Marcos Oliveira;Rafael Nóbrega;Jenny Ormanns;Werner Kloas;Romain Feron;Christophe Klopp;Hugues Parrinello;Laurent Journot;Shunping He;John Postlethwait;Axel Meyer;Yann Guiguen;Manfred Schartl
  • 通讯作者:
    Manfred Schartl
Evolution of soxE genes in teleost fish revealed by comparative expression analysis and genomics
通过比较表达分析和基因组学揭示硬骨鱼 soxE 基因的进化
  • DOI:
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hayato Yokoi;Yi-Lin Yan;Ayano Miyagi;Mark Currey;Julian Catchen;William Cresko;Tohru Suzuki;John Postlethwait
  • 通讯作者:
    John Postlethwait
Medaka : Model for Organogenesis, Human Disease and Evolution.
青鳉:器官发生、人类疾病和进化模型。
  • DOI:
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hayato Yokoi;John Postlethwait
  • 通讯作者:
    John Postlethwait

John Postlethwait的其他文献

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{{ truncateString('John Postlethwait', 18)}}的其他基金

ANT LIA: The Role of Sex Determination in the Radiation of Antarctic Notothenioid Fish
ANT LIA:性别决定在南极诺托类鱼类辐射中的作用
  • 批准号:
    2232891
  • 财政年份:
    2023
  • 资助金额:
    $ 36万
  • 项目类别:
    Standard Grant
EAGER: Origin and Physiological Consequences of a Neoplasm Outbreak in Antarctic Fish
EAGER:南极鱼类肿瘤爆发的起源和生理后果
  • 批准号:
    1947040
  • 财政年份:
    2020
  • 资助金额:
    $ 36万
  • 项目类别:
    Standard Grant
Antarctic Fish and MicroRNA Control of Development and Physiology
南极鱼类和 MicroRNA 对发育和生理的控制
  • 批准号:
    1543383
  • 财政年份:
    2016
  • 资助金额:
    $ 36万
  • 项目类别:
    Standard Grant
The Non-Vertebrate Chordate Oikopleura and Evolution of Vertebrate Developmental Innovations
非脊椎动物脊索动物 Oikopleura 和脊椎动物发育创新的进化
  • 批准号:
    0719577
  • 财政年份:
    2007
  • 资助金额:
    $ 36万
  • 项目类别:
    Standard Grant
IGERT Proposal - Integrated Training in the Evolution of Development
IGERT 提案——发展演变中的综合培训
  • 批准号:
    0504627
  • 财政年份:
    2005
  • 资助金额:
    $ 36万
  • 项目类别:
    Continuing Grant
The Non-vertebrate Chordate Oikopleura and Evolution of Vertebrate Developmental Innovations
非脊椎动物脊索动物 Oikopleura 和脊椎动物发育创新的进化
  • 批准号:
    0345203
  • 财政年份:
    2004
  • 资助金额:
    $ 36万
  • 项目类别:
    Continuing Grant
Genetic Basis of Morphological Evolution in Stickleback
刺鱼形态进化的遗传基础
  • 批准号:
    0236239
  • 财政年份:
    2003
  • 资助金额:
    $ 36万
  • 项目类别:
    Continuing Grant
IGERT Formal Proposal:Integrated Training in the Evolution of Development
IGERT正式提案:发展演变中的综合培训
  • 批准号:
    9972830
  • 财政年份:
    1999
  • 资助金额:
    $ 36万
  • 项目类别:
    Continuing Grant

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Conference: 2023 Molecular Mechanisms in Evolutions GRC and GRS: Genetic and Phenotypic Evolution at the Organismal, Cellular and Molecular Levels
会议:2023进化中的分子机制GRC和GRS:有机体、细胞和分子水平的遗传和表型进化
  • 批准号:
    2328755
  • 财政年份:
    2023
  • 资助金额:
    $ 36万
  • 项目类别:
    Standard Grant
Deciphering molecular genetic mechanisms underlying chromatin interactions
破译染色质相互作用的分子遗传机制
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    DE220101210
  • 财政年份:
    2023
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    $ 36万
  • 项目类别:
    Discovery Early Career Researcher Award
Genetic and molecular mechanisms of Xbp-1 mediated salivary gland development and differentiation
Xbp-1介导唾液腺发育和分化的遗传和分子机制
  • 批准号:
    10678146
  • 财政年份:
    2023
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    $ 36万
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A novel genetic mutation reveals the molecular and cellular mechanisms of severe recurrent skin inflammation
一种新的基因突变揭示了严重复发性皮肤炎症的分子和细胞机制
  • 批准号:
    10679177
  • 财政年份:
    2023
  • 资助金额:
    $ 36万
  • 项目类别:
Genetic, molecular, and neural mechanisms of alcohol-induced effects on sleep
酒精对睡眠影响的遗传、分子和神经机制
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    10591406
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    2022
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Genetic and molecular mechanisms of Nf1-dependent neuronal regulation of metabolism
Nf1 依赖性神经元代谢调节的遗传和分子机制
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    10418360
  • 财政年份:
    2022
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  • 项目类别:
Analyzing genetic and environmental molecular mechanisms causing autoimmune thyroid diseases
分析导致自身免疫性甲状腺疾病的遗传和环境分子机制
  • 批准号:
    10693959
  • 财政年份:
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Genetic and molecular mechanisms of kidney stone disease
肾结石疾病的遗传和分子机制
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    MR/W03168X/1
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Analyzing genetic and environmental molecular mechanisms causing autoimmune thyroid diseases
分析导致自身免疫性甲状腺疾病的遗传和环境分子机制
  • 批准号:
    10517531
  • 财政年份:
    2022
  • 资助金额:
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Genetic and molecular mechanisms of Nf1-dependent neuronal regulation of metabolism
Nf1 依赖性神经元代谢调节的遗传和分子机制
  • 批准号:
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