Neurobiology of vertebrate reproduction: the granin-derived neuropeptide secretoneurin is a new reproductive hormone

脊椎动物生殖神经生物学：谷物衍生神经肽促泌神经素是一种新的生殖激素

• 批准号: RGPIN-2021-03174
• 负责人: Trudeau, Vance
• 金额: $ 8.81万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745593
• 关键词: Neurobiology; vertebrate; reproduction; granin; derived

Acquiring new knowledge about hormones that control animal reproduction is the main goal of my research. Environmental signals such as light and temperature can regulate reproduction by changing the activities of genes that themselves are responsible for hormone production in the body. My laboratory made the compelling discovery of a new sex hormone called secretoneurin. In fish there are 2 forms of this hormone, which we named secretoneurin a and secretoneurin b. They are the short peptides resulting from specific degradation of larger protein products of the secretogranin-2a and 2b genes. Using the CRISPR/Cas9 gene editing technology, we created zebrafish with one or both secretogranin-2 genes deleted. These unique models will allow my group to determine the functions of this novel hormone system. The sexual behaviour of these fish will be studied and compared to normal animals. Experiments with isolated tissues and injections of synthetic version of secretoneurin will lead us to determine how and when secretoneurin stimulates reproduction by examining effects on the brain, pituitary gland, ovaries and testes. We will study transgenic fish whose neurons and pituitary cells are marked with fluorescent proteins. This will lead to the discovery of how they communicate with other cells. A new method called single cell RNA sequencing will be employed to fully characterize and classify the cell types producing secretoneurin. A major challenge we will undertake is the identification the secretoneurin receptor. We would then determine the role of the receptor in reproduction, driving our research to the next level. The structure of secretoneurin is very similar between different vertebrate animals. The knowledge gained from research on fish may help us understand reproduction control mechanisms in other animals, for example in frogs or humans. On a more practical scale, the expected results may have applications for controlled reproduction in aquaculture. Importantly, young scientists will receive training in state-of-the art techniques in a dynamic and inclusive research environment. They will use genome editing techniques for fish, RNA sequencing and bioinformatics, and proteomics (a high-powered method to measure hundreds of proteins at one time). These highly qualified personnel will be encouraged to present at national and international conferences, mentored on career development and will publish their results in scientific journals. They will be highly sought after by academia, industry, or government research departments.

获得有关控制动物繁殖的激素的新知识是我研究的主要目标。光和温度等环境信号可以通过改变基因的活动来调节生殖，这些基因本身负责体内荷尔蒙的产生。我的实验室令人信服地发现了一种名为分泌神经元的新性激素。在鱼类中，这种激素有两种形式，我们将其命名为分泌神经素a和分泌神经素b。它们是分泌颗粒素-2a和2b基因的较大蛋白产物特异性降解的短肽。利用CRISPR/Cas9基因编辑技术，我们培育出了缺失一个或两个分泌型颗粒素-2基因的斑马鱼。这些独特的模型将使我的团队能够确定这种新的激素系统的功能。这些鱼的性行为将被研究，并与正常动物进行比较。通过分离组织和注射合成版本的分泌神经磷酸酶的实验，我们将通过检测对大脑、脑下垂体、卵巢和睾丸的影响来确定分泌神经磷酸酶如何以及何时刺激生殖。我们将研究其神经元和脑垂体细胞被荧光蛋白标记的转基因鱼类。这将导致发现它们是如何与其他细胞通信的。一种名为单细胞RNA测序的新方法将被用来完全表征和分类产生分泌神经磷酸酶的细胞类型。我们将面临的一个主要挑战是分泌神经磷酸酶受体的鉴定。然后，我们将确定受体在生殖中的作用，将我们的研究推向下一个水平。不同脊椎动物之间的分泌神经磷酸酶结构非常相似。从对鱼的研究中获得的知识可能有助于我们了解其他动物的生殖控制机制，例如青蛙或人类。在更实际的规模上，预期结果可能应用于水产养殖的受控繁殖。重要的是，年轻科学家将在充满活力和包容性的研究环境中接受最先进的技术培训。他们将使用FISH、RNA测序和生物信息学的基因组编辑技术，以及蛋白质组学(一种同时测量数百种蛋白质的高性能方法)。将鼓励这些高素质人员出席国内和国际会议，指导他们的职业发展，并将在科学期刊上发表他们的成果。他们将受到学术界、工业界或政府研究部门的高度追捧。