PUB - Publikationen an der Universität Bielefeld

The thesis aims to elucidate the role of transforming growth factor-β (TGFβ) signalling in microglia and the regulation of Smad4-mediated microglial functions, and their subsequent impact on central nervous system (CNS) homeostasis, neurodevelopment, and neuroinflammation. The study comprehensively describes the TGFβ signalling pathway in microglia, analyzing the intracellular dynamics of TGFβ-associated proteins, the interaction and subcellular distribution of Smads, and the cross-talk between different TGFβ superfamily receptors. It also delineates the canonical and non-canonical TGFβ signalling in microglia and the effect of lipopolysaccharide (LPS)-induced reactive state on microglia TGFβ signalling. Advanced gene expression profiling techniques, such as Nanostring nCounter technology, were utilized to examine microglia-specific gene expression during development and under LPS and TGFβ signalling inhibition. The epigenetic basis for microglia-specific gene expression during early postnatal development was also analyzed. The thesis further investigates the effect of Smad4 deletion in microglia on CNS cellular populations and the microenvironment within the brain. It elucidates the role of Smad4-mediated TGFβ signalling in the regulation of microglial functions during early postnatal development and in adults, as well as in response to inflammatory stimuli. The findings of this thesis provide valuable insights into the intricacies of TGFβ signalling in microglia and its importance in maintaining CNS homeostasis, neurodevelopment, and regulating neuroinflammatory responses. The study highlights the critical role of Smad4 in mediating the effects of TGFβ signalling on microglia and the subsequent impact on the CNS landscape.