Regulation of neurogenesis by Cux factors and their interacting proteins.

Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Multiple Sclerosis, and Amyotropic Lateral Sclerosis, along with brain injury are devastating conditions that are associated with the decline of the brain function. Due to our aging population, the frequency of these illnesses is rapidly increasing in Canada. We have very limited treatment options for these conditions, thus there is an urgent need to develop new therapeutics to overcome neurodegeneration. A common feature of neurodegenerative diseases is the severe loss of neurons in affected individuals. One exciting avenue for therapeutics is to stimulate the brain to make new neurons to replace those lost to injury or illness. The adult brain has considerable plasticity and continually generates neurons from neural stem cells in two principal regions: the hippocampus, and the subventricular zone, which supplies neurons to the olfactory region. If we wish to use the brain's endogenous ability to make new neurons, we must first seek to understand the molecular and cellular mechanisms that regulate the formation of new neurons. To that end I have identified a group of regulatory proteins called Cux factors that are expressed in neural stem cells of the embryonic and postnatal brain. It is currently unclear whether these proteins play a role in regulating the formation of neurons in the postnatal brain. Thus a primary objective of this proposal to explore the roles of Cux genes in the formation of neurons in the adult brain using mice that have been engineered to lack these proteins. I have also identified a network of proteins that interact with Cux factors and will examine their roles in the formation of neurons. The goal of the research described in this proposal is to understand how the formation of new neurons in the adult brain is regulated by these Cux factors. This in turn will lead to ways in which we can stimulate neuronal repair in diseased and injured brains.