IOS: RUI: Investigation of the Role of a Receptor Protein Tyrosine Phosphatase in Synaptic Partner Recognition

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In the last century, a large number of neural circuits in the brain and throughout the body have been described. These neural circuits mediate such critical functions as perception and behavior. However, we understand much less about the genes involved in building these circuits. This project will use a unique fluorescent marker to visualize synaptic contacts between specific neurons in live nematodes, allowing us to advance our understanding of neural circuit formation by investigating the role of a conserved cell surface molecule. The broader impact of this project is to encourage students to develop critical thinking skills through the use of the scientific process. Toward that goal, the project will include direct participation of undergraduate and Master's-level researchers; mentorship of a community college professor in genetics research during the summer; and development of modules for a new course, which will include datagenerated by this research project. In addition, the PI has and will continue to actively seek to increase participation of underrepresented minorities and women in science through these activities.Much is known about early steps in neural circuit formation, including the migration of neuronal cell bodies and axons to the correct regions of the body. Much less is known about how neurons recognize the correct partners from the many potential partners they may encounter in a target region. This project will utilize the trans-synaptic split-GFP based marker, NLG-1 GRASP (Neuroligin-1-mediated GFP Reconstitution Across Synaptic Partners), to visualize synaptic contacts between individual neurons of interest in live animals. NLG-1 GRASP, together with a circuit-specific behavioral assay to assess synaptic function, will be used to characterize the novel role of a conserved receptor protein tyrosine phosphatase (RPTP) in synaptic partner recognition. Further work will determine which domains are required for RPTP function. Finally, genes that function with this RPTP will be identified and studied, with the goal of elucidating anew synaptic partner recognition pathway. The primary intellectual merit of this research is advancing our understanding of the mechanisms that underlie the specificity of neural circuit formation.