The role of TAO2 in brain connectivity and Autism Spectrum Disorders
Autism spectrum disorders (ASDs) are neurodevelopmental disorders in which individuals have disrupted social communication and repetitive stereotyped behaviors, which lead to life-long difficulties. Approximately 1% of individuals in Asia, North America and in Europe have an ASD, which demonstrates the need to better understand these disorders, and find effective treatments to improve quality of life. In this regard, one of the key discoveries in recent years is that a persons genetic blueprint plays a very important role in risk for ASDs. This means that there are genetic risk factors for ASD, and understanding how these genes cause abnormal brain development will help us to better understand the origins of ASDs to develop better treatments. In the current grant, using an integrated approach, we propose to study the TAO2 gene, which is either missing or duplicated in individuals with ASD. Our group is already collaborating with the Autism Sequencing Consortium to discover new mutations in TAO2 that may cause ASD, which will aid future development of more accurate genetic diagnoses of ASDs. We will complement this hunting for mutation approach with cellular and molecular studies to better understand the normal function of TAO2 in the development of brain connections and autism-related behaviors in mouse models. Additionally, we will determine how mutations in TAO2, found in ASD individuals, may contribute to abnormal brain connectivity. We aim at studying the exciting possibility that another ASD-linked gene named FMR1 may control the function of TAO2. We believe this will lead to the identification of a new autism genetic pathway in the brain that would ultimately allow the discovery of drugs that, through TAO2 modulation, would ameliorate deficits observed in patients with ASD. Ultimately, we believe our studies will be very important not only to understand how TAO2 regulates brain function but also how it may be causative of ASDs via the novel FMRP-TAO2 genetic pathway.
Gene targeting in the brain, Autism, Imaging techniques, Electrophisiological approaches, Behavioural methodologies, aetiology, omics approaches
2014 - 2017
Froylan Calderon de Anda (Coordinator)