Developmental Axon Pruning Requires Destabilization of Cell Adhesion by JNK Signaling

Developmental axon pruning is essential for normal brain wiring in vertebrates and invertebrates. How axon pruning occurs in vivo is not well understood. In a mosaic loss-of-function screen, we found that Bsk, the Drosophila JNK, is required for axon pruning of mushroom body γ neurons, but not their dendrites. By combining in vivo genetics, biochemistry, and high-resolution microscopy, we demonstrate that the mechanism by which Bsk is required for pruning is through reducing the membrane levels of the adhesion molecule Fasciclin II (FasII), the NCAM ortholog. Conversely, overexpression of FasII is sufficient to inhibit axon pruning. Finally, we show that overexpressing other cell adhesion molecules, together with weak attenuation of JNK signaling, strongly inhibits pruning. Taken together, we have uncovered a novel and unexpected interaction between the JNK pathway and cell adhesion and found that destabilization of cell adhesion is necessary for efficient pruning. •Bsk, the Drosophila JNK, is required for axon, but not dendrite, pruning of MB neurons•Bsk negatively regulates FasII membrane stability and/or residence to promote pruning•Overexpression of the FasII adhesion molecule is sufficient to inhibit axon pruning•Upregulation of cell adhesion molecules inhibits axon pruning Bornstein et al. describe a novel and unexpected interaction between the JNK pathway and cell adhesion in regulating developmental axon pruning. They show that destabilization of the cell adhesion molecule Fasciclin II is necessary for efficient axon pruning.