Journal Article

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

Chen, Jiakun, Freeman, Marc R, Poskanzer, Kira E, Monk, Kelly R

2020

Overview

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.Chen et al. define previously unreported zebrafish astrocytes, provide new insights into vertebrate astrocyte development and lay the foundation for studying astrocyte function in the entire nervous system of an intact and behaving animal.

• Publisher: Nature Publishing Group
• Subject: Astrocytes / Calcium ions / Circuits / CRISPR / Danio rerio / Fibroblast growth factor receptor 4 / Fibroblast growth factor receptors / Glial cells / Glutamate-ammonia ligase / Glutamine / In vivo methods and tests / Morphogenesis / Nervous system / Neural networks / Norepinephrine / Radial glial cells / Stem cells / Synapses / Vertebrates / Zebrafish