UNC-40/DCC receptor was originally identified as an axon guidance molecule, and has been shown to regulate cell migration and neuronal polarization. We identified an unexpected role for UNC-40/DCC as a regulator of presynaptic assembly. How can the same receptor and ligand pair elicit axon guidance or presynaptic assembly in a cell-specific manner? We are using genetic and molecular approaches to answer this question.
In particular, we are focusing on the newly identified capacity of the UNC-40/DCC receptor to direct presynaptic assembly. We are conducting structure/function studies aimed at identifying domains important for UNC-40 synaptogenic function in the AIY interneuron. Determining the roles of different UNC-40 domains will be critical for understanding how UNC-40/DCC specifies correct synaptic location in the AIY interneuron and how this function relates to its conventional role as a guidance molecule. We are also using genetic approaches to identify the signal transduction pathways that lead to the assembly of presynaptic terminals. Our preliminary data suggest that the UNC-40-mediated axon guidance and presynaptic assembly pathways are genetically separable. Given how conserved the Netrin pathway is across metazoans, and the importance of UNC-40/DCC in coordinating the innervation of circuits in the nematode brain, we expect our studies will be relevant to our future understanding on how these signaling pathways could be utilized in the innervation of more complex circuits, such as those found in vertebrate brains.