dock8 deficiency attenuates microglia colonization in early zebrafish larvae

Microglia are tissue-resident macrophages that carry out immune functions in the brain. The deficiency or dysfunction of microglia has been implicated in many neurodegenerative disorders. DOCK8, a member of the DOCK family, functions as a guanine nucleotide exchange factor and plays key roles in immune regulation and neurological diseases. The functions of DOCK8 in microglia development are not fully understood. Here, we generated zebrafish dock8 mutants by CRISPR/Cas9 genome editing and showed that dock8 mutations attenuate microglia colonization in the zebrafish midbrain at early larvae stages. In vivo time-lapse imaging revealed that the motility of macrophages was reduced in the dock8 mutant. We further found that cdc42/cdc42l, which encode the small GTPase activated by Dock8, also regulate microglia colonization in zebrafish. Collectively, our study suggests that the Dock8-Cdc42 pathway is required for microglia colonization in zebrafish larvae.

Automated summary

In this study, we generated zebrafish dock8 mutants using CRISPR/Cas9 and found that dock8 mutations attenuate microglia colonization in the zebrafish midbrain. Time-lapse imaging revealed reduced motility of macrophages in the dock8 mutants. We also discovered that cdc42/cdc42l genes, which encode the small GTPase activated by Dock8, regulate microglia colonization in zebrafish.