Chromatin regulation by BAF complex controls cortical astrogenesis

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“Astrocytes constitute the largest cell population in the human brain and are crucial for the brain development. Defects in astrogenesis are linked with neurological disorders such as Rett syndrome, fragile X syndrome, and brain tumors. Therefore, it is important to understand how astrocytes are generated.The chromatin remodeling SWI/SNF (SWItch/Sucrose NonFermentable) complex, also known as BAF (Brg1/Brm Associated Factors) complex, plays an essential role in brain development, however, its function in astrogenesis is largely unknown. Our expression analysis indicated that two paralog subunits BAF155 and BAF170 are expressed in all known murine cortical astrocyte sources such as late cortical progenitors (E17.5-E18.5) of the ventricular zone (VZ), adult neural stem cells (aNSCs) in the subventricular zone (SVZ) and dentate gyrus (DG), and dividing astrocytes (also known as astrocyte precursors) in the cortical layers of juvenile mice. In addition, our preliminary proteomic data indicates that the both BAF subunit interacts in vivo with key factors, which were known to play a key role in astrogenesis.The primary aim of this proposal is to characterize the astrocytic phenotypes of BAF155 and BAF170 mutant mice. Secondly, we aim to study the BAF155 and BAF170-dependent mechanisms that control astrocytic development by applying a combination of genomic, proteomic approaches, advanced imaging and genetic manipulation techniques. This study would provide valuable insights into the molecular mechanism, which is mediated by the mSWI/SNF chromatin remodeling complex that controls astrogenesis”.