Project 447344

Genetic studies to identify the cause of neurodevelopmental disorders have increasingly implicated several chromatin remodelling factors among other genes. Mutations in one such gene - chromodomain, helicase, DNA binding (CHD) 7, are the major cause of a neurodevelopmental disorder called CHARGE syndrome (CS) and have been associated with autism spectrum disorders (ASD). CHD7 is a member of DNA binding proteins and has well-documented roles in regulating gene expression. However, the neuropathological mechanisms underlying the autistic features in CS and ASD upon CHD7 mutations remain unknown. 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. 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 ASDs. It may also provide important insights to later develop pharmacological interventions that will prevent or reverse neurological defects in CS.