Postnatal maturation of microglia is associated with alternative activation and activated TGFß signaling.

ABSTRACT

Microglia are involved in a widespread set of physiological and pathological processes and further play important roles during neurodevelopmental events. Postnatal maturation of microglia has been associated with the establishment of microglia-specific gene expression patterns. The mechanisms governing microglia maturation are only partially understood but Tgfß1 has been suggested to be one important mediator. In the present study, we demonstrate that early postnatal microglia maturation is associated with alternative microglia activation, increased engulfment of apoptotic cells as well as activated microglial Tgfß signaling. Interestingly, microglial Tgfß signaling preceded the induction of the microglia-specific gene expression indicating the importance of Tgfß1 for postnatal microglia maturation. Moreover, we provide evidence that Tgfß1 is expressed by neurons in postnatal and adult brains defining neuron-microglia communication via Tgfß1 as an important event. Finally, we introduce the recently identified microglia marker Tmem119 as a direct Tgfß1-Smad2 target gene. Taken together, the data presented here further increase the understanding of Tgfß1-mediated effects in microglia and place emphasis on the importance of Tgfß1 for microglia maturation and maintenance.