Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction.

ABSTRACT: Microglia play a pivotal role in the coordination of brain development and have emerged as a critical determinant in the progression of neurodegenerative diseases; however, the role of microglia in the onset and progression of neurodevelopmental disorders is less clear. Here we show that conditional deletion of αVβ8 from the central nervous system (Itgb8ΔCNS mice) blocks microglia in their normal stepwise development from immature precursors to mature microglia. These "dysmature" microglia appear to result from reduced TGFβ signaling during a critical perinatal window, are distinct from microglia with induced reduction in TGFβ signaling during adulthood, and directly cause a unique neurodevelopmental syndrome characterized by oligodendrocyte maturational arrest, interneuron loss, an

SUBMITTER: Arnold TD 

PROVIDER: S-EPMC6446869 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature