Funding outcome

During child development, neural stem cells are responsible for producing all the different cell types that build the brain. In broad terms, brain is composed of grey and white matter. Grey matter is primarily composed of nerve cells, the main signalling cell types. However, white matter is essential for nerve cells to properly communicate with one another. Aberrations in brain communication and connectivity are believed to be the main underlying pathology in paediatric neurodevelopmental disorders, such as autism. An emerging way to restore brain connectivity is to repair the white matter, which is otherwise aberrant in patients and mouse models of neurodevelopmental disorders, autism and schizophrenia. How can we do this? Neural stem cells that exist in pediatric and adult brain are capable of making the building blocks of white matter, cells termed oligodendrocytes. Oligodendrocytes are the only brain cells that produce myelin, a fatty substance that gives white appearance in the white matter. If we could understand what causes neural stem cells to become oligodendrocytes in a healthy developing brain, we can begin to develop therapies that engage existing neural stem cells for the treatment and/or prevention of cognitive and behavioural deficiencies seen in children with neurodevelopmental disorders. I will investigate whether fractalkine, an immunological molecule present in the developing brain, can instruct neural stem cells to become oligodendrocytes. To do this, I will use mice as a model organism. I will investigate oligodendrocyte and myelin formation in neural stem cells i) grown in the presence of fractalkine; ii) lacking fractalkine signalling pathway; and iii) activated with fractalkine in pre-clinical mouse model. If successful, I will translate my findings to a 'human development model in a dish' by using stem cells derived from human skin (induced pluripotent cells). We hope that the results from this project will lay the groundwork to investigating fractalkine as a therapeutic agent in treating or preventing pediatric neurodevelopmental disorders.