Cellular and molecular mechanisms of Akirin2 function in maturing neurons

For the brain to function properly, it needs an assortment of cell types that all have a different function. The genes expressed in each cell determines its identity and provides instructions for its function. Disruption of these genes can cause the cell to lose its identity, malfunction, and die. To prevent cell death in the brain and to better understand what these cells need to function properly, it is important to understand what mechanisms control gene expression in these cells.

Our lab studies a protein called Akirin2 that controls gene expression in several cell types but had never been studied in the brain. We previously found that if you prevent developing brain cells in the embryonic cortex from making Akirin2, this region of the brain fails to form. Without Akirin2, cortical precursor cells stop dividing, mature too quickly, and die. My studies expand upon this work by showing that Akirin2 is also essential for the survival of mature brain cells, long after this developmental period. My work demonstrates that Akirin2 suppresses a protein called p53, which controls genes that tell the cell to stop dividing or to undergo cellular suicide. Without Akirin2 to suppress this death-promoting protein, these brain cells express the wrong genes and die as the animals age. This work highlights the importance of gene regulation in the brain, provides a comprehensive view of the genes critical for brain cell survival, and identifies cellular pathways regulated by Akirin2 as potential players in neurodegenerative disorders such as Alzheimer’s disease.