RESUMEN
Microglia diversity emerges from interactions between intrinsic genetic programs and environment-derived signals, but how these processes unfold and interact in the developing brain remains unclear. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) expressed in radial glia progenitors activates microglia-expressed TGFß1, permitting microglial development. Domain-restricted deletion of Itgb8 in these progenitors establishes complementary regions with developmentally arrested "dysmature" microglia that persist into adulthood. In the absence of autocrine TGFß1 signaling, we find that microglia adopt a similar dysmature phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the TGFß signal transducers Smad2 and Smad3 have a less polarized dysmature phenotype and correspondingly less severe neuromotor dysfunction. Finally, we show that non-canonical (Smad-independent) signaling partially suppresses disease and development associated gene expression, providing compelling evidence for the adoption of microglial developmental signaling pathways in the context of injury or disease.
RESUMEN
Disparities in prostate cancer (PCa) exist at all stages: screening, diagnosis, treatment, outcomes, and mortality. Although there are a multitude of complex biological (e.g., genetics, age at diagnosis, PSA levels, Gleason score) and nonbiological (e.g., socioeconomic status, education level, health literacy) factors that contribute to PCa disparities, nonbiological factors may play a more significant role. One understudied aspect influencing PCa patients is mental health related to the quality of life. Overall, PCa patients report poorer mental health than non-PCa patients and have a higher incidence of depression and anxiety. Racial disparities in mental health, specifically in PCa patients, and how poor mental health impacts overall PCa outcomes require further study.