Immune regulation of neuronal stem cells in the medaka retina.

Stem cell populations in tissues require precise regulation of their number and quality to maintain proper organ growth. Among the various regulatory mechanisms, immune cells are emerging to directly regulate stem cell populations. The medaka retinal stem cell (RSC) niche, a model for lifelong neurogenic growth, provides a system for studying immune-stem cell interactions. We investigate how microglia, which are resident macrophages of the central nervous system, regulate the RSC niche. We identify that bona fide RSCs express the chemokine Ccl25b, while its cognate receptor, Ccr9a, is expressed in microglia. These microglia form a surveillance ring adjacent to the RSC niche and actively phagocytose RSCs. Interference with microglia by deletion of spi1b reveals that microglia absence leads to increased numbers of ccl25b-positive RSCs and results in morphological defects of the retina. Targeted mutation of ccl25b specifically affects microglia mobility under injury conditions; however, we did not observe any morphological defects, indicating that Ccl25b-Ccr9a signaling is not essential for stem cell maintenance. Overall, our data show that, under homeostatic conditions, the individual RSCs, which are essential for proper eye development, are actively phagocytosed by immune surveillance.