Microglia influence during central nervous system (CNS) inflammation and injury is an active area of research. However, new research has shown microglia begin to invade the embryo brain around embryonic (e) day 10.5 in mouse, suggesting a unique role for these yolk-sac derived immune cells in CNS development. Although the role of microglia in brain development in utero is just starting to be explored, early reports suggest microglia can influence neurodevelopmental processes such as progenitor maintenance and cell differentiation. Our overall research is focused on asking three questions: (1) what are the microglia populations present during development; (2) what mechanisms direct and attract microglia towards the developing fetal brain; (3) what functional role does microglia play in the developing hypothalamus.
I systematically identify timing of microglia invasion into the developing hypothalamus and microglia activation state using fluorescent imaging approaches. The developing hypothalamus is an excellent system to study microglia invasion and microglia-cell interactions due to its easily identifiable progenitor zone and readily available markers that label distinct nuclei and neuronal populations used to define the spatiotemporal timing of microglia invasion in the developing tuberal hypothalamus. Specifically, pregnant mice were sacrificed and embryonic brain tissue was harvested on e11.5, e13.5, e15.5 and e17.5. Cryosectioned brains were labeled with microglia and hypothalamic markers for fluorescent imaging followed by stereological analyses employed to quantify the hypothalamic microglia population. We show microglia invade the hypothalamus starting at e11.5 and align with hypothalamic progenitors near the end of neurogenesis. Combined, these data suggest a possible role for microglia in maintaining hypothalamic progenitor populations given their pivotal position during development, where they can interact with progenitors. Defining the role of microglia during normal fetal development will allow for a better understanding of how in utero perturbations can affect microglia function during key windows in embryonic development.