Abstracts
Using Neural Stem Cells to Discover Origins of Brain Disorders and Therapeutics
Lachlan Jolly
PhD Student, Discipline of Biochemistry, Adelaide University
Supervised through CHRI
2-3% of children suffer from Mental Retardation (MR), the origins of which usually trace back to genetic alterations which affect the child's fetal brain development. The earliest brain tissue to arise in development consists of a population of Neural Stem Cells (NSCs), which are the precursor cells from which the entire brain and nervous systems are derived. Dysfunction of NSCs causes a variety of brain disorders, thus knowledge of the genes controlling NSC function are of great importance, providing insights into the origins of such disorders. Additionally, development of techniques by which NSCs can be expanded in the laboratory provides an invaluable tool for the discovery of drug and cell replacement therapies giving hope to the treatment of brain disorders. We proposed that the gene USP9x might provide a link between NSC function and MR because we found high levels of USP9x in stem cells, and USP9x is mutated in patients with MR, and additionally implicated in other brain disorders including epilepsy. Thus we sought to discover the function of USP9x in NSCs. By elevating the activity of USP9x in NSCs, we found that NSCs rapidly expanded in number by changing the way in which they divided, and the mature cell types they could produce. This provides substantial insight into the brain disorders associated with USP9x, as well as the ways in NSCs grow and divide. The discoveries can be used to manipulate NSCs in the laboratory, enhancing their use in the development of drug and cellular therapies.
