Neurons form synapses with remarkable specificity both at the cellular and subcellular level. However, the molecular mechanisms underlying the synaptic specificity is not well understood. Here we use C. elegans AIY interneuron as a model to address this question. AIY forms presynapses with distinct and highly reproducible pattern: the ventral region proximal to soma without synapse (Zone 1), the turn region from the ventral to the dorsal fragment with enriched synapses (Zone 2) and the distal region with a few scattered synapses (Zone 3). We found that the receptor tyrosine kinase ROR/CAM-1 is required for AIY synaptic specificity. Cam-1 regulates AIY presynaptic spacial specificity through the opposite roles in synaptogenesis: it promoters synapse formation at the synaptic enriched region (Zone 2) and suppresses synaptogenesis at the asynaptic region (Zone 1). To determine the temporal role of
cam-1, we monitored the dynamic change of the synaptic pattern during different development stages. We found that
cam-1 act during both embryonic and larval stages. Further study indicated that the prosynaptogenesis role is mediated through wnt pathway:
cwn-2/cfz-2/dsh-2/sys-1. While the antisynaptogenesis role of CAM-1 is independent of any known wnt receptors, Disheveled or beta -catenin. We conclude that ROR/CAM-1 regulates synaptic spacial specificity through opposite functions in synaptogenesis mediated by distinct signaling pathways.