Grant: Project Grant

The ependymal cells (EC) lining the walls of brain ventricles play an essential role in brain health and physiology. They form a barrier between cerebrospinal fluid (CSF) and underlying neural tissue, and possess motile cilia that constantly beat to circulate CSF ensuring the passage of nutrients and removal of waste products. They also surround adult neural stem cells (NSCs) and regulate their function. Intriguingly, it is still unknown how the cilia beating of EC is regulated and whether neuronal activity controls the rate and efficiency of cilia beating, that in turn regulate CSF flow and NSCs activity. In this project using mouse models, advanced imaging and genetic tools, in vivo monitoring of NSCs activity and live imaging of EC cilia beating, we will study mechanisms regulating EC cilia beating and whether they impact the transition of NSCs from their dormant, quiescent to activated, proliferative state. We will also investigate the differentiation potential of NSCs and distinct cell types that they generate after modulation of EC cilia beating. Our study will lead to better understanding of the mechanisms regulating EC cilia beating, CSF flow, and maintenance of stem cells quiescence and proliferation. This, in turn, will provide new strategies to sustain brain health and metabolism by regulating CSF flow and "turn on" brain regenerative capacity by modulating adult NSCs function.