Fragile X syndrome is a developmental brain disorder with abnormal neuron architecture and functional plasticity of the developing brain. It is the most commonly inherited form of both mental retardation and autism spectrum disorders (ASD). The proposed research will use the fruit fly as a model organism to study the molecular and cellular basis of disease, focusing particularly on the role of the Fragile X Mental Retardation Protein (FMRP). Various methods will test whether FMRP is required during a certain period of time in neural development and will assess the protein's role in synaptic neurotransmission during brain neural circuit development. Additionally, proteomic screens will determine the presence or absence of FMRP during specific periods of brain development. Forward genetics will be used to identify genes that interact with the dfmr1 gene to cause the disease phenotype. This proposal directly tests therapeutic interventions aimed at correcting ASD-relevant brain developmental abnormalities, and future studies could lead to promising drug therapies for people with fragile X or other autism-related disorders.