Project 450834

CHARGE syndrome (CS) is a rare genetic disorder affecting about 1 in 10,000 newborns. It is caused by mutations in the CHD7 gene and is associated with neurodevelopmental disorders such as intellectual disability, attention deficit disorder with or without hyperactivity, seizure and autistic behaviour. Additionally, mutations in CHD7 have been associated with autism spectrum disorder (ASD), a developmental disorder that affects communication and behaviour. However, the cause of the manifestation of neurological symptoms upon CHD7 mutations in CS and ASD remain unknown. CHD7 is a protein that regulates gene expression. I therefore hypothesize that CHD7 regulates genes that are crucial for proper neural network development, input balance and maintenance in the brain. To test this, we will capitalize on the strength of a simple genetic model - the zebrafish and examine the role of CHD7 in the development of neural networks in the brain using innovative approaches. We will also investigate the molecular effects of CHD7 on the brain to identify genes that it regulates. This proposed research plan will enhance our understanding of brain defects in CS and ASD. It may also provide important insights to later develop pharmacological interventions that will prevent or reverse neurological defects in CS.