Elucidating mechanisms of microglial tiling

In a process called tiling, homeostatic microglia homogenously organize in a grid-like fashion to achieve efficient surveillance of the brain. The molecular mechanisms underlying tiling are unknown. I hypothesize that microglia use cell-surface proteins to sense density of neighboring microglia, thereby contributing to constant cell-to-cell distances. I will use in situ proximity labeling and mass spectrometry in a model of microglial repopulation to identify key cell-surface proteins involved in regulating density, then perform a genetic screen in a human stem cell model to determine the proteins’ individual contributions to tiling. This study will advance knowledge of basic homeostatic microglial functions.