The role of TAOK2 in neuronal migration

• Applicant: Dr. Froylan Calderon de Anda
• Subject Area: Developmental Neurobiology ; Biological Psychiatry
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 434353741

Studies using human postmortem brain tissue and mouse models of autism spectrum disorders (ASD) have revealed anatomical differences in the brains of autistic individuals. These include the presence of ill-defined neocortical cellular layers (layering defects) and abnormal structure and function of dendritic spines (sites of synapses). While it is likely that these developmental brain defects contribute to disease expression, it is not known which signaling pathways regulate these abnormalities. This information is critical because it is a necessary precursor to the development of targeted drug therapies.The current proposal focuses on a gene named thousand-and-one-amino acid serine/threonine protein kinase 2 (TAO2), which lies in the ASD-associated copy number variation (CNV) at chromosome 16p11.2. TAO2 was recently shown to regulate cortical dendrite formation and is of particular interest because it is a direct target of the RNA binding protein Fragile X Mental Retardation Protein (FMRP; encoded by the FMR1 gene), which is absent or mutated in the most common form of inherited mental retardation. Given this, we are testing the exciting hypothesis that TAO2 regulates neuronal migration and thus define a new ASD signaling pathway that regulates brain connectivity and behavioral abnormalities. We are encouraged by the success of our preliminary studies and are seeking funding from DFG to further develop this project.

• DFG Programme: Research Grants
• Co-Investigator: Melanie Richter, Ph.D.