Social signals that regulate C. elegans development

调节线虫发育的社会信号

• 批准号: 9976542
• 负责人: Ilya Ruvinsky
• 金额: $ 33.18万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9976542
• 关键词: Address; Affect; Age; Animal Model; Animals; Behavior; Biological Models; Biology; Caenorhabditis elegans; Cells; Chemicals; Congenital Abnormality; Defect; Development; Disease; Ensure; Environment; Evolution; Exposure to; Female; Genes; Genetic; Germ Cells; Gonadal structure; Health; Heritability; Hermaphroditism; Human; Individual; Insulin; Lead; Mammals; Modeling; Molecular; Neurons; Neurosecretory Systems; Organism; Pathology; Pathway interactions; Phenotype; Physiology; Play; Population; Process; Production; Quantitative Genetics; Regulation; Reproduction; Reproductive Physiology; Research; Resolution; Role; Serotonin; Shapes; Signal Transduction; Social Environment; Social Interaction; System; Transforming Growth Factor beta; Work; age related; cost; experimental study; female reproductive system; flexibility; germline stem cells; human disease; insight; male; neural circuit; neuronal cell body; neuronal circuitry; reproductive; reproductive function; response; sex; sexual identity; social; stem cell population; trait

PROJECT SUMMARY Organismal development is a highly regulated process; its dysregulation can lead to disease. Yet, it is also flexible to make it responsive to the environment. One aspect of the environment is the social interactions among organisms. Whereas it is generally understood that these are important, the specific ways in which they affect organisms remain substantially unknown. Recent estimates, however, suggest that the impact of social interactions could be comparable in magnitude to the effect of genes. This necessitates the development of tractable model systems in which to study this problem. We addressed this challenge by studying the effects of social signals on development of a well-established model organism, C. elegans. We found that signals produced by males powerfully affect development and reproductive physiology of hermaphrodites, which are effectively female. Specifically, sensing the male presence alters hermaphrodite germline development, ensuring higher quality of gamete production until older age. Our experiments uncovered that these processes are controlled by highly conserved neuroendocrine signals that include insulins and serotonin. Taking advantage of the specific strengths of our model system and these preliminary findings we will investigate: (1) The specific developmental changes that take place in the germline and the gonad that supports it; (2) How neurons communicate the receipt of social signals to the gonad, where they affect the germline development; and (3) The role of behavior and sexual identity of neurons in responding to social signals appropriately. Importantly, although we study these problems in C. elegans, strikingly similar phenomena have been documented in all animals studied so far, including mammals. Moreover, defects neuroendocrine control of reproduction and sexual identity of cells have been implicated in numerous human disease conditions. This raises a possibility that social signals might play a role in their pathology. A better mechanistic understanding of these processes would lead to a better understanding of the underlying biology of these disease states. Because all molecular components we identified so far are highly conserved among all animals, we expect our work will offer insights for further research on the role of social signals in regulation of development and physiology. It may thus prove useful for a better understanding and, ultimately, treatment of relevant disease states in humans.

项目摘要 器官发育是一个高度调节的过程;其失调可导致疾病。然而，它也是 使其灵活地适应环境。环境的一个方面是社会互动 在有机体中。虽然人们普遍认为这些是重要的，但它们的具体方式 受影响的生物体仍然基本上未知。然而，最近的估计表明， 相互作用的大小可以与基因的影响相媲美。这就需要发展 一个简单的模型系统来研究这个问题。我们通过研究 社会信号的发展，一个完善的模式生物，C。优美的我们发现信号 雄性产生的激素对雌雄同体的发育和生殖生理有很大的影响， 有效的女性。具体来说，感知男性的存在会改变雌雄同体的生殖系发育， 确保更高质量的配子生产，直到老年。我们的实验发现这些过程 由高度保守的神经内分泌信号控制，包括胰岛素和血清素。以 利用我们的模型系统的具体优势和这些初步研究结果，我们将调查：（1） 生殖系和支持生殖系的性腺发生的特定发育变化;（2）如何 神经元将社会信号的接收传达给性腺，在那里它们影响生殖细胞的发育; （3）神经元的行为和性别认同在对社会信号做出适当反应中的作用。 重要的是，虽然我们在C中研究这些问题。与此惊人相似的现象 迄今为止研究的所有动物，包括哺乳动物。此外，缺陷的神经内分泌控制 细胞的生殖和性别特征与许多人类疾病有关。这 提出了一种可能性，即社会信号可能在他们的病理中发挥作用。更好的机械理解 这些过程的研究将有助于更好地了解这些疾病状态的潜在生物学。 由于我们迄今为止鉴定的所有分子组分在所有动物中都是高度保守的，我们希望我们的 这项工作将为进一步研究社会信号在调节发展中的作用提供见解， physiology.因此，它可能有助于更好地了解并最终治疗相关疾病 人类的国家。