" TGF-beta and sensory regulation of germline development in C. elegans".

“TGF-β 和线虫种系发育的感觉调节”。

• 批准号: 8342070
• 负责人: E. Jane Albert Hubbard
• 金额: $ 32.2万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8342070
• 关键词: Address; Afferent Neurons; Animals; Binding; Caenorhabditis elegans; Cell Proliferation; Cells; Couples; Cues; Development; Distal; Environment; Environmental Risk Factor; Equilibrium; Failure; Fertility; Food; Genetic Transcription; Germ Cells; Germ Lines; Goals; Health; Human; Ligands; Link; Mediating; Modality; Modeling; Molecular; Nervous system structure; Neurons; Neurosecretory Systems; Notch Signaling Pathway; Pathway interactions; Phenotype; Pheromone; Play; Population; Population Density; Production; Receptor Signaling; Regulation; Regulatory Element; Reporting; Reproduction; Role; Sensory; Signal Pathway; Signal Transduction; Skiing; Somatic Cell; Specific qualifier value; Stem cells; System; Testing; Time; Trans-Activators; Transcriptional Regulation; Transforming Growth Factor beta; Travel; Work; base; intercellular communication; meetings; mutant; notch protein; novel; progenitor; promoter; receptor; response; stem; stem cell niche

DESCRIPTION (provided by applicant): The balance of proliferation and differentiation in stem and progenitor cell populations must meet organismal needs. However, molecular mechanisms that mediate this balance are poorly understood. For germ cells, this correlation is particularly vital since the failure to produce sufficient germ cell progenitors is deleterious for fertility. We recently discovered that the environment can influence on germ cell development via sensory modalities that act through neurons. We found that TGF? signaling influences the stem cell "proliferation versus differentiation" decision in the C. elegans germ line at a critical time when it is expanding its stem cell pool. We found that DAF- 7/TGF? exerts its effects on the germ line in response to specific sensory cues and through two specific neurons that report the favorability of the environment. We also found that the TGF? receptor pathway acts in the germline stem cell niche, not the germ line. TGF? signaling thereby couples fertility to the quality of the environment by acting through the stem cell niche. In this proposal we address the regulation of the TGF? in response to the environment, and mechanisms downstream of the TGF? receptor that ultimately transmit information to the germ line. PUBLIC HEALTH RELEVANCE: Environmental factors impact reproduction. This application follows from our surprising discovery that the environment can influence fertility by way of chemosensory neurons and a conserved TGF? signaling pathway in C. elegans. Our studies will likely benefit human health since the cellular and molecular mechanisms underlying these controls are evolutionarily conserved.

描述(由申请人提供)：干细胞和祖细胞群体中的增殖和分化的平衡必须满足组织的需要。然而，调节这种平衡的分子机制却知之甚少。对于生殖细胞来说，这种相关性尤其重要，因为不能产生足够的生殖细胞前体细胞对 生育能力。我们最近发现，环境可以通过通过神经元作用的感觉模式来影响生殖细胞的发育。我们发现了转化生长因子？信号影响线虫生殖系干细胞“增殖还是分化”的关键时刻 是时候扩大其干细胞库了。我们发现DAF-7/转化生长因子？对特定的感官提示作出反应，并通过两个报告环境有利的特定神经元，对胚系施加影响。我们还发现转化生长因子？受体途径作用于生殖系干细胞，而不是生殖系。转化生长因子？因此，通过干细胞生态位的作用，信号将生育力与环境质量联系在一起。在这项提案中，我们解决了对转化生长因子的监管？应对环境，以及下游的转化生长因子的作用机制？最终将信息传递给生殖系的受体。 公共卫生相关性：环境因素影响生殖。这一应用源于我们令人惊讶的发现，即环境可以通过化学感觉神经元和保守的转化生长因子？线虫中的信号通路。我们的研究可能有益于人类健康，因为这些控制的细胞和分子机制在进化上是保守的。