Deciphering the roles of microglia plasticity and diversity in brain development and disorders.

Microglia, resident immune cells of the brain, fulfil multiple and contrasting functions in the brain from its development throughout the entire lifespan under normal conditions, but also in the context of brain disorders.

How can the microglia be multitasking?The prevailing view in the field remains that microglia are highly plastic cells that acquire different reactive states and functions when exposed to extrinsic cues in their environment.

However, emerging evidence, including from our team, indicates that the microglial cell population exhibits several cellular subsets with unique intrinsic properties.

Hence, we argue that the plasticity of microglia, i.e., microglia reactive states, as well as the inherent diversity of microglia, i.e., the microglia subtypes, must be considered to understand the multitasking microglia.We aim at elucidating the molecular events, which control the acquisition of microglia reactive states exerting unique functions in the healthy or pathologic brain.

We also propose to uncover the microglia subtypes that co-exist within the developing brain, characterize the programs that regulate their intrinsic phenotypes and unique functions, and thereafter establish their contribution to brain development and disorders throughout life.We are convinced that increased knowledge of microglia plasticity and diversity will provide a platform for novel innovative therapeutic strategies to combat devastating disorders of the developing and the mature brain.