Trans-synaptic Fish-lips Signaling Prevents Misconnections between Non-synaptic Partner Olfactory Neurons

Abstract

Significance StatementIn 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.

Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits

“…Several LRRs regulate synaptic target specificity in Drosophila. They include Toll proteins (9 paralogs), capricious (2 paralogs), connectin (Kurusu et al, 2008;Nose et al, 1992Nose et al, , 1997Shishido et al, 1998), and Fili (Xie et al, 2019). For example, Toll regulates targeting of motoneuron axons to innervate appropriate muscles.…”

“…Here, Toll/Toll homophilic interactions appear to be repulsive in nature; loss of function mutations result in innervation of incorrect targets (Halfon et al, 1995;Rose et al, 1997). Toll 6 and Toll 7 regulate the targeting of different subclasses of olfactory receptor neurons to their appropriate projection neuron targets (Ward et al, 2015) and Fili is required in projection neurons (PNs) to prevent inappropriate targeting of axons to specific glomeruli (Xie et al, 2019) (Figure 10). Capricious patterns projection neuron dendrites in the glomeruli of the antennal (olfactory) lobe and also regulates targeting of R8 growth cones in the visual system (Shinza-Kameda et al, 2006;Hong et al, 2009).…”