美国俄勒冈健康与科学大学Kelly R. Monk和Jiakun Chen团队合作取得最新进展。他们对斑马鱼神经回路中星形胶质细胞形态发生和功能进行实时成像。该研究于2020年9月7日发表于《自然-神经科学》。

他们表征斑马鱼细胞类型与哺乳动物星形胶质细胞非常相似，后者源自放射状神经胶质细胞，并在幼体早期建立其环境的复杂过程。斑马鱼的星形胶质细胞与突触紧密结合，彼此平铺并表达标记物，包括Glast和谷氨酰胺合成酶。一旦整合到回路中，它们就会表现出对去甲肾上腺素敏感的全细胞和微域Ca2 +瞬变。

最后，使用细胞特异性CRISPR–Cas9方法，他们证明了脊椎动物星形胶质细胞形态发生需要fgfr3和fgfr4。这项工作提供了从体内干细胞到有丝分裂后星形胶质细胞形态发生的首次可视化，确定了脊椎动物星形胶质细胞中Fgf受体的作用，并将斑马鱼确立为研究体内星形胶质细胞生物学的有价值的新模型系统。

据了解，星形胶质细胞如何生长以及如何整合到神经回路中仍然不清楚。斑马鱼非常适合此类研究，但该系统尚未描述真正的星形胶质细胞。

附：英文原文

Title: Live-imaging of astrocyte morphogenesis and function in zebrafish neural circuits

Author: Jiakun Chen, Kira E. Poskanzer, Marc R. Freeman, Kelly R. Monk

Issue&Volume: 2020-09-07

Abstract: How astrocytes grow and integrate into neural circuits remains poorly defined. Zebrafish are well suited for such investigations, but bona fide astrocytes have not been described in this system. Here we characterize a zebrafish cell type that is remarkably similar to mammalian astrocytes that derive from radial glial cells and elaborate processes to establish their territories at early larval stages. Zebrafish astrocytes associate closely with synapses, tile with one another and express markers, including Glast and glutamine synthetase. Once integrated into circuits, they exhibit whole-cell and microdomain Ca2+ transients, which are sensitive to norepinephrine. Finally, using a cell-specific CRISPR–Cas9 approach, we demonstrate that fgfr3 and fgfr4 are required for vertebrate astrocyte morphogenesis. This work provides the first visualization of astrocyte morphogenesis from stem cell to post-mitotic astrocyte in vivo, identifies a role for Fgf receptors in vertebrate astrocytes and establishes zebrafish as a valuable new model system to study astrocyte biology in vivo.

DOI: 10.1038/s41593-020-0703-x

Source: https://www.nature.com/articles/s41593-020-0703-x