Microglia-specific expression of Olfml3 is Directly regulated by Transforming growth Factor β1-induced smad2 signaling

Microglia maturation takes place during the postnatal weeks and is characterized by the establishment of a unique microglia-specific gene expression pattern. Tmem119, Fcrls, Hexb, and Olfml3 have been identified among these microglia-specific genes. Transforming growth factor beta 1 (TGF beta 1) has been reported as a critical factor for microglia maturation and maintenance and active TGF beta signaling precedes the inductions of microglial gene expression. In this study, we demonstrate Olfml3 expression in adult microglia and further provide evidence that TGF beta 1 induces upregulation of Olfml3 expression in postnatal microglia. Using chromatin immunoprecipitation and microglia-specific silencing of TGF beta signaling in vitro and in vivo, we in clearly show that Olfml3 is a direct TGF beta 1/Smad2 target gene. Together, our data underline the importance of TGF beta 1 as a critical regulator of microglia functions and microglia maturation and further broaden our understanding of TGF beta 1-mediated effects on the resident immune cells of the central nervous system.