Funding outcome

The brain is a remarkable organ that has a limited capacity to regenerate diverse cells thanks to resident neural stem cells (NSCs). Postnatal and adult NSCs are capable of producing oligodendrocytes (OL) throughout life. Oligodendrocytes are specialized brain cells that produce myelin, an insulating material that ensures efficient neuronal propagation, a major component of brain white matter. Production of OL and myelin is important for learning and cognition. In agreement, children with neurodevelopmental and autism spectrum disorders display anomalies in myelin and oligodendrocytes. These anomalies in myelin structure can predict autism in children prior to the onset of symptoms. Finally, restoring myelin levels rescues behavioural deficits in a mouse model of neurodevelopmental Williams syndrome. Thus, oligodendrocyte formation represents an excellent pharmacological target for neurodevelopmental disorders (reviewed in Watson et al. 2020 Neurosci Lett). Dr. Voronova identified in the embryonic brain, a specific type of neurons secrete factors that instruct NSCs to form oligodendrocytes (Voronova et al. 2017 Neuron). One of these predicted factors is hepatoma-derived growth factor (HDGF). My results generated over previous summer and undergraduate research projects indicate that HDGF increases oligodendrocyte production from cultured NSCs. However, the ability of HDGF to engage resident postnatal NSCs for oligodendrocyte production in vivo is not known. To address this, I will assess whether HDGF treatment of pre-clinical mouse model of NSC engagement leads to enhanced oligodendrocyte and myelin production.