Immune surveillance and pruning 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 and regenerative capacity. Amongst various regulatory mechanisms, immune cells are emerging to directly regulate stem cell populations. The medaka retinal stem cell niche, a model for lifelong neurogenic growth, provides a system to study immune cell-stem cell interactions. Here we investigate how microglia, the resident macrophages of the central nervous system, regulate the retinal stem cell niche. We identify that bona fide retinal stem cells express the chemokine ccl25b while its cognate receptor, ccr9a, is expressed in microglia. These microglia form a surveillance ring adjacent to the stem cell niche and actively phagocytose retinal stem cells. Interference with microglia by deletion of spi1b reveals that microglia absence leads to increased numbers of ccl25b-positive stem cells and results in morphological defects in the retinal stem cell niche and 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 retinal stem cell population, essential for proper eye development, is actively pruned by immune surveillance.