Microglia originate in the yolk sac and invade the brain at early embryonic development. Then, driven by proliferation, microglial progenitors colonize all the parenchyma until they reach their final density and position, reaching a mosaic-like distribution (3D tessellation). However, how this adult tessellation is orchestrated remains to be elucidated. In the first part of the talk, I will present our preliminary data on how microglia tessellation is orchestrated using an agent-based mathematical model to simulate microglia tessellation and discover the laws that govern this process. In the second part of my talk, I will focus on another unexplored aspect of microglial development: the role of neuronal activity. We have recently identified a key developmental milestone in microglia: the synchronic switch from proliferative to mitotically quiescent cells, which occurs around postnatal day 5 in the hippocampus. Interestingly, this developmental switch coincides with the developmental GABA switch from excitatory to inhibitory, prompting us to test if the GABA switch influences microglial maturation using bumetanide, an inhibitor of the NKCC1 chloride transporter responsible for the GABA switch. To test if NKCC1 blockade is sensed by microglia we performed two-photon imaging of acute slices from P2 and P14 postnatal mice. Unexpectedly, bumetanide only had an effect in P14 microglia, suggesting that ability of microglia to respond to NKCC1 blockade emerges later in development. Understanding how microglia tessellate the brain, and the drivers of microglial maturation can be useful to develop novel tools such as brain organoids and can provide novel insights about neurodevelopmental disorders.