Our nervous system is a network of neuronal circuits that mediate perception, behavior, and thought. To form circuits, neurons must identify their correct synaptic partners among the many neurites in a target region, and proceed to form synapses. Elucidating the molecular mechanisms neurons employ to identify the correct partners and build synapses may help us to gain a better understanding of neurological disorders including autism and schizophrenia. To study synaptic partner recognition, we utilize a transgenic trans-synaptic marker called Neuroligin 1-mediated GFP Reconstitution Across Synaptic Partners (NLG-1 GRASP), which fluorescently labels synapses between specific sets of neurons in live animals. Utilizing this marker, our group previously found that the secreted UNC-6/Netrin ligand and its canonical receptor UNC-40/DCC regulate synaptic partner recognition between PHB sensory neurons and AVA interneurons in C. elegans. Our current research focuses on identifying molecules that may act downstream of these recognition molecules, to target synaptic components and assemble synapses. We have tested a panel of molecules required for synapse formation in other neurons and in other organisms. We found that two genes involved in axon outgrowth and synapse formation,
rpm-1/Highwire and
unc-69/SCOCO, are both required for normal PHB axon extension. In both mutants, the region of contact between PHB sensory neurons and AVA interneurons is significantly reduced. Interestingly,
rpm-1/Highwire mutants have normal PHB-to-AVA synapses, while
unc-69/SCOCO mutants have severely reduced PHB-to-AVA synapses. This suggests that defects in synapse formation observed in
unc-69/SCOCO may not be caused by defects in axon length. We are currently testing additional molecules to further elucidate the synaptic partner recognition pathway and placing them in order using molecular and genetic analysis. Our ultimate goal is to elucidate the entire pathway from recognition of synaptic partners to synaptic assembly and maintenance.