Radial-glial stem cell development and plasticity in the adult zebrafish brain

成年斑马鱼大脑中放射状胶质干细胞的发育和可塑性

• 批准号: RGPIN-2019-05357
• 负责人: Lindsey, Benjamin
• 金额: $ 2.19万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738219
• 关键词: Radial; glial; stem; cell; development

The long-term objective of my research program is to understand adult neural stem cell activity in the central nervous system of vertebrates. Most animals retain lifelong populations of adult neural stem cells in subregions of the brain, commonly known as the `neurogenic niche'. These cells produce newborn neurons throughout the life of animals, and in mammals and birds appear to play an important role in animal behaviour, learning and memory. In recent years, it has been discovered that different populations of adult neural stem cells react differently to various forms of stimuli or injury. This has proposed that adult neural stem cell populations located in different neurogenic niches may contribute to distinct functions in order to keep the central nervous system in balance. Very little however is understood towards how different populations of adult neural stem cells behave over development or under different biological contexts. This is particularly true in leading fish models, such as the zebrafish and medaka, which maintain some of the largest populations of adult neural stem cells and diversity of neurogenic niches. The proposed research will use the zebrafish model to study the activity of radial-glial brain stem cells across separate neurogenic niches and under different biological conditions. The zebrafish provides a valuable experimental system to examine these questions, owing to its adult neurogenic niches in brain structures that process both cognitive and sensory information, and remarkable neuro-regenerative potential. How populations of radial-glia change as neurogenic niches take on an adult form remains unclear. I will identify the dynamic changes in radial-glial populations from larval to adult stages and how these changes may be controlled at the molecular level. While other vertebrates, such as rodents, show a direct link between adult neural stem cells and learning species-specific behaviours, it is unknown whether this holds true in fish models. I will address this question by examining whether radial-glial populations are required to perform learning tasks in adult zebrafish. Finally, to better understand the activity of similar radial-glial stem cell types in different neurogenic niches and under different contexts, I will define radial-glial behaviour and gene regulation following enrichment and injury. Collectively, the proposed research will advance our fundamental knowledge of adult neural stem cell activity in teleost models while training at least 9 HQP. My work will serve to broaden our understanding of adult neural stem cell activity beyond the small number of vertebrates studied to date, and identify mechanisms in the zebrafish that may be present in cell populations of the central nervous system across major vertebrate and invertebrate groups. This will be important for moving towards a comparative and evolutionary understanding of the lifelong role and regulation of neural stem cells.

我的研究项目的长期目标是了解脊椎动物中枢神经系统中成体神经干细胞的活动。大多数动物在大脑的次区域中保留终身的成体神经干细胞群，通常称为“神经原性龛”。这些细胞在动物的整个生命过程中产生新生神经元，在哺乳动物和鸟类中似乎在动物行为，学习和记忆中发挥重要作用。近年来，人们发现不同群体的成体神经干细胞对各种形式的刺激或损伤的反应不同。这表明，位于不同神经源性小生境的成体神经干细胞群可能有助于不同的功能，以保持中枢神经系统的平衡。然而，人们对不同群体的成体神经干细胞在发育过程中或在不同生物学背景下的行为知之甚少。这在领先的鱼类模型中尤其如此，例如斑马鱼和青鳉，它们保持了一些最大的成体神经干细胞群体和神经源性生态位的多样性。 拟议的研究将使用斑马鱼模型来研究放射状神经胶质脑干细胞在不同神经原性龛和不同生物条件下的活性。斑马鱼提供了一个有价值的实验系统来研究这些问题，因为它在大脑结构中处理认知和感觉信息的成年神经源性小生境，以及显着的神经再生潜力。神经原性小生境呈现成人形式时，放射状神经胶质细胞的数量如何变化仍不清楚。我将确定放射状神经胶质细胞群体从幼虫到成人阶段的动态变化，以及如何在分子水平上控制这些变化。虽然其他脊椎动物，如啮齿动物，显示出成体神经干细胞和学习物种特异性行为之间的直接联系，但尚不清楚这是否适用于鱼类模型。我将解决这个问题，研究是否需要径向神经胶质细胞的人口在成年斑马鱼执行学习任务。最后，为了更好地了解类似的放射状神经胶质干细胞类型在不同的神经源性龛和不同的情况下的活动，我将定义放射状神经胶质细胞的行为和基因调控富集和损伤后。 总的来说，拟议的研究将推进我们对硬骨鱼模型中成体神经干细胞活动的基础知识，同时训练至少9个HQP。我的工作将有助于拓宽我们对成体神经干细胞活性的理解，超越迄今为止研究的少数脊椎动物，并确定斑马鱼中可能存在于主要脊椎动物和无脊椎动物群体中枢神经系统细胞群中的机制。这将是重要的走向比较和进化的理解神经干细胞的终身作用和调节。