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Live-imaging of astrocyte morphogenesis and function in zebrafish neural circuits.
Nature Neuroscience ( IF 25.0 ) Pub Date : 2020-09-07 , DOI: 10.1038/s41593-020-0703-x
Jiakun Chen 1 , Kira E Poskanzer 2, 3 , Marc R Freeman 1 , Kelly R Monk 1
Affiliation  

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.



中文翻译:

斑马鱼神经回路中星形胶质细胞形态发生和功能的实时成像。

星形胶质细胞如何生长并整合到神经回路中的定义仍然不明确。斑马鱼非常适合此类调查,但该系统中尚未描述真正的星形胶质细胞。在这里,我们描述了一种斑马鱼细胞类型,这种细胞类型与哺乳动物星形胶质细胞非常相似,这些星形胶质细胞来源于放射状神经胶质细胞,并精心设计了在早期幼虫阶段建立其领地的过程。斑马鱼星形胶质细胞与突触密切相关,彼此平铺并表达标记,包括Glast和谷氨酰胺合成酶。一旦集成到电路中,它们就会表现出对去甲肾上腺素敏感的全细胞和微域 Ca 2+瞬变。最后,使用细胞特异性 CRISPR-Cas9 方法,我们证明了fgfr3fgfr4是脊椎动物星形胶质细胞形态发生所必需的。这项工作首次展示了星形胶质细胞在体内从干细胞到有丝分裂后星形胶质细胞的形态发生,确定了 Fgf 受体在脊椎动物星形胶质细胞中的作用,并将斑马鱼作为一种有价值的新模型系统来研究体内星形胶质细胞生物学。

更新日期:2020-09-08
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