斑馬魚作為研究星形膠質細胞的新模型

斑馬魚作為研究星形膠質細胞的新模型

作者：

小柯機器人

發布時間：2020/9/9 17:30:24

美國俄勒岡健康與科學大學Kelly R. Monk和Jiakun Chen團隊合作取得最新進展。他們對斑馬魚神經迴路中星形膠質細胞形態發生和功能進行實時成像。該研究於2020年9月7日發表於《自然-神經科學》。

他們表徵斑馬魚細胞類型與哺乳動物星形膠質細胞非常相似，後者源自放射狀神經膠質細胞，並在幼體早期建立其環境的複雜過程。斑馬魚的星形膠質細胞與突觸緊密結合，彼此平鋪並表達標記物，包括Glast和穀氨醯胺合成酶。一旦整合到迴路中，它們就會表現出對去甲腎上腺素敏感的全細胞和微域Ca2 +瞬變。

最後，使用細胞特異性CRISPR–Cas9方法，他們證明了脊椎動物星形膠質細胞形態發生需要fgfr3和fgfr4。這項工作提供了從體內幹細胞到有絲分裂後星形膠質細胞形態發生的首次可視化，確定了脊椎動物星形膠質細胞中Fgf受體的作用，並將斑馬魚確立為研究體內星形膠質細胞生物學的有價值的新模型系統。

據了解，星形膠質細胞如何生長以及如何整合到神經迴路中仍然不清楚。斑馬魚非常適合此類研究，但該系統尚未描述真正的星形膠質細胞。

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