Development and molecular phenotypes of zebrafish astrocytes

星形胶质细胞是人脑中主要的胶质细胞类型，对中枢神经系统(CNS)至关重要。 发展和功能。星形胶质细胞功能障碍与人类神经发育和 精神疾病。鉴于星形胶质细胞在中枢神经系统发育和健康中扮演的重要角色，这是令人惊讶的 人们对星形胶质细胞成熟的分子和细胞机制知之甚少 与相邻细胞的功能相互作用。对当前可用的模型系统的一个警告是无法 操纵和观察活的、完整的动物中星形胶质细胞的发育和动态变化。透明 斑马鱼的幼体非常适合于这样的研究，但骨的星形胶质细胞还没有在 到目前为止，这个系统。在这里，我们的目标是利用斑马鱼幼体的光学透明度与分子 和遗传方法来表征斑马鱼中一种新的神经胶质细胞类型，这种细胞具有 哺乳动物星形胶质细胞。我们在斑马鱼中枢神经系统中发现了一种以前未报道的细胞类型，有几个 确定哺乳动物星形胶质细胞的特征，如错综复杂的浓密形态，谷氨酸转运体 表达，以及自发的微域钙瞬变。在本提案中，我们将：1)充分说明 斑马鱼星形胶质细胞的发育和功能；2)建立细胞特异性CRISPR/Cas9方法 活体内星形细胞生物学。我们期待我们的工作将斑马鱼作为一种新的模式系统进行探索 星形胶质细胞的发育和功能，为分子和细胞机制提供了新的见解 调控星形胶质细胞的发育和生长，为研究星形胶质细胞的功能奠定基础 在一只完好无损和行为正常的动物身上。

Astrocytes are the major glial cell type in the human brain and are critical for central nervous system (CNS) development and function. Astrocyte dysfunction has been implicated in human neurodevelopmental and psychiatric diseases. Given the important roles astrocytes play in CNS development and health, it is surprising that little is known about the molecular and cellular mechanisms that govern astrocyte maturation and their functional interactions with neighboring cells. One caveat for currently available model systems is the inability to manipulate and observe astrocyte development and dynamic changes in living, intact animals. Transparent zebrafish larvae would be ideally suited for such studies, but bone fide astrocytes have not been described in this system to date. Here, we aim to exploit the optical transparency of zebrafish larvae together with molecular and genetic approaches to characterize a new glial cell type in zebrafish that features key hallmarks of mammalian astrocytes. We have identified a previously unreported cell type in zebrafish CNS with several defining characteristics of mammalian astrocytes, such as intricate bushy morphology, glutamate transporter expression, and spontaneous microdomain Ca2+ transients. In this proposal, we will: 1) fully characterize the development and function of astrocytes in zebrafish; 2) develop a cell-specific CRISPR/Cas9 method to study astrocyte biology in vivo. We expect our work will establish zebrafish as a new model system to explore astrocyte development and function, provide new insights into the molecular and cellular mechanisms regulating astrocyte development and growth, and lay the foundation to study astrocyte function in the context of the entire nervous system in an intact and behaving animal.