Modeling critical neurodevelopmental periods and underlying time-critical signaling networks of autism spectrum disorders in patient-derived neurons

• Applicant: Dr. Simon Schäfer
• Subject Area: Biological Psychiatry ; Developmental Biology ; Developmental Neurobiology ; Cell Biology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318857726

Neural development is a time-dependent process, which includes many different consecutive events such as cell fate specification, axon and dendrite development and synapotogenesis. Autism represents a complex neurodevelopmental disorder that has been shown to involve abnormal acceleration of brain growth with early overgrowth and later normalization. Although autism spectrum disorders (ASDs) appear to be highly heritable overall, their underlying genetic etiology is complex involving many genes. This complexity is particularly relevant when designing functional studies without knowing where and when to investigate the respective risk mutation in the brain. Consequently, rather than focusing on individual risk genes, designing a temporal approach on the dynamics of maturational signaling networks within defined cell populations may be beneficial to understand developmental differences in ASDs. The aim of this study is to compare the developmental trajectory of human neurons derived from autistic and control individuals using different reprogramming technologies starting from neural stem cell divisions and proceeding through neuronal morphogenesis and maturation. The use of next-generation sequencing methods, such as transcriptome profiling in combination with functional analyses of single cells within their defined developmental stage, could provide a powerful tool to compare active signaling networks at a given time during development. This approach may provide a comprehensive insight into maturational differences and affected signaling pathways in ASDs as part of a potential spatiotemporal convergence among the groups of disease-related mutations. Furthermore, this study is aimed to unravel critical neurodevelopmental periods and to investigate to which extend a possible developmental heterochrony in ASD may affect mature neuronal function and plasticity.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Fred H. Gage