Systemic and local control of neural stem cell quiescence and reactivation

Most of the brain’s stem cells spend their time in a reversible, dormant state called quiescence, and this project will map the molecular chain of events that wakes them up to make new neurons. The problem is that after injury or in neurodegenerative disease, the brain’s own stem cells often fail to reactivate and repair the damage. Researchers know that signals from other organs—such as the gut or blood—can trigger these cells to start dividing, but the precise sequence of molecular steps from a systemic signal all the way down to a single cell’s genome is unknown. Without that map, it is impossible to design therapies that reliably coax dormant stem cells into action. This is fundamental science. The project uses fruit flies to trace, in a living animal, how a signal travels from one organ to the brain, through the tissue, into the cell, and finally to the genes that switch on proliferation. There is no immediate clinical application. However, similar fundamental work on stem cell control in other tissues has already led to new approaches for regenerating blood and gut lining. A complete molecular roadmap of neural stem cell reactivation could eventually make it possible to regenerate neurons after stroke, spinal cord injury, or in conditions like Parkinson’s disease.