Grant: Project Grant

Collectively, traumatic and degenerative brain injuries afflict millions of Canadians, and burden society at both the human and financial levels. Since the human brain has very little regenerative capacity, injury typically leads to permanent deficits. Harnessing the regenerative potential of neural stem cells represents one of the only approaches with the promise of restoring function to treat these conditions. However, the complexity of the brain represents a formidable barrier to the fulfilment of this goal. In order to develop effective cell replacement therapies, we need to greatly improve our understanding of how brain circuits are generated during development, so that we can generate the appropriate types of cells. During brain development, stem cells must give rise to a multitude of different cell types in order to generate a fully functional nervous system. Stem cells must tightly regulate the expression of thousands of genes in order to generate the diversity of neurons and glia found in the brain. This process is very poorly understood. We have recently identified a gene called Casz1 that appears to play an important role in this process. We hypothesize that Casz1 coordinates gene expression to limit and control the types of cells that a neural stem cell can produce. We propose to study the precise biological pathway that Casz1 uses to do this, using the developing retina as a model system. We anticipate that this work will shed light on the mechanism through which neural stem cells regulate their potential, which should allow us to control and tailor their output for regenerative medicine. By improving our knowledge of how neural stem cells behave during brain development, we also anticipate that this study may provide insights into congenital neurodevelopmental disorders.