PLEXINS AND MOLECULAR MECHANISMS OF AXON GUIDANCE

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DESCRIPTION (provided by applicant): The nervous system consists of an intricate network of neuronal connections. The formation of proper connections during development is the essential first step in building a functional nervous system. The overall goal of this study is to understand the molecular mechanisms that guide axons to find their appropriate targets. Gene targeting techniques, in vitro molecular binding experiments, and in vitro neuronal cultures will be used to study specific functional role of axon guidance molecules. The specific aims of this proposal are: (1) to study the specific functions of plexins by analyzing the axon guidance phenotypes in plexin knockout mice, (2) to characterize the interactions of plexins by analyzing the phenotypes in double knockout mice and by studying the in vitro biochemical interactions, and (3) to explore the role of plexins in stereotyped axon pruning by analyzing the pruning phenotypes in plexin knockout mice and by establishing in vitro axonal branch pruning assays. This research will help us understand how axon guidance molecules function together to ensure that during the development of the nervous system no errors occur in the formation of the initial neuronal network. More generally, defects in forming appropriate axonal connections are likely to cause many neurodevelopmental disorders, such as autism, schizophrenia, synesthesia and mental retardation. Understanding the molecular mechanisms could revolutionize our ability to characterize and treat these developmental disorders.