Funding outcome

The brain is an extraordinarily complex organ, and the process by which ii is constructed during development is an extremely complicated one that is still not completely understood. What is known, however, is that neural stem cells (NSCs) are the primary building blocks of the brain, and that they must very carefully differentiate into the right cell types in the right places and at the right times during brain development. Disruptions to this highly precise process may result in wide variety of effects such as abnormal brain function, and it is believed that such disruptions are a major cause of autism spectrum disorder (ASD) and other neurodevelopmental disorders. There are three main cell fates for NSCs: neurons, astrocytes, and oligodendrocytes. The proposed research project deals with the formation of oligodendrocytes, which are the only source of myelin in brain white matter. Myelin is important for overall brain health as it insulates neurons and ensures efficient neuronal communication. OJigodendrocytes and/or myelin formation is perturbed in neurodevelopmental disorders like ASD and schizophrenia, as well as in pediatric neurological disorders like leukodystrophy. It is therefore important to understand how NSCs become oligodendrocytes. Dr. Voronova's research has shown that special kinds of neurons called interneurons are responsible for this process through a molecule called fractalkine. The research, of which I played a role. showed that fractalkine signalling directly affects embryonic NSCs and oligodendrocyte formation. Furthermore, scientific literature has shown that fractalkine signalling disruption are present in patients with ASD and schizophrenia, and that genetically-modified mice with perturbed fractalkine signalling show ASDlike symptoms. Thus, it is possible that ASD may arise in part due to aberrant oligodendrocyte formation in fractalkine signalling deficient patients. We wish to further understand how fractafkine signalling functions in embryonic NSCs during brain development and how perturbations in fractalkine signalling lead to aberrant neural development and ASD. In addition, we want to test if fractalkine can promote oligodendrocyte formation from postnatal NSCs. These are a known source of oligodendrocyte formation after birth and represent an excellent target for development and testing of pro-oligodendrocyte formation therapies from NSCs.