RT Journal Article SR Electronic T1 Trans-synaptic Fish-lips Signaling Prevents Misconnections between Non-synaptic Partner Olfactory Neurons JF bioRxiv FD Cold Spring Harbor Laboratory SP 600064 DO 10.1101/600064 A1 Qijing Xie A1 Bing Wu A1 Jiefu Li A1 Hongjie Li A1 David J Luginbuhl A1 Chuanyun Xu A1 Xin Wang A1 Liqun Luo YR 2019 UL http://biorxiv.org/content/early/2019/04/04/600064.abstract AB Our understanding of the mechanisms of neural circuit assembly is far from complete. Identification of new wiring molecules with novel mechanisms of action will provide new insights into how complex and heterogeneous neural circuits assemble during development. Here, we performed an RNAi screen for cell-surface molecules and identified the leucine-rich-repeat containing transmembrane protein, Fish-lips (Fili), as a novel wiring molecule in the assembly of the Drosophila olfactory circuit. Fili contributes to the precise targeting of both olfactory receptor neuron (ORN) axons as well as projection neuron (PN) dendrites. Cell-type-specific expression and genetic analyses suggest that Fili sends a trans-synaptic repulsive signal to neurites of non-partner classes that prevent their targeting to inappropriate glomeruli in the antennal lobe.Significance Statement In the fruit fly olfactory system, 50 classes of olfactory receptor neurons (ORNs) make precise synaptic connections with 50 classes of corresponding projection neurons (PNs). Identification of wiring molecules in this circuit can provide insight into understanding neural circuit assembly. This paper reports the role of a transmembrane protein, Fish-lips (Fili), in forming specific connections in this circuit. We found that some ORN axons are repelled by Fili, which is present on dendrites of non-matching PN class, preventing them from targeting inappropriate glomeruli. Similarly, some PN dendrites are repelled by Fili expressed by non-matching ORN class for their correct targeting. Together, these results suggest that Fili mediates repulsion between axons and dendrites of non-synaptic partners to ensure precise wiring patterns.