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

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, includingGlastand glutamine synthetase. Once integrated into circuits, they exhibit whole-cell and microdomain Ca(2+)transients, which are sensitive to norepinephrine. Finally, using a cell-specific CRISPR-Cas9 approach, we demonstrate thatfgfr3andfgfr4are 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.