Developmental Axon Pruning Requires Destabilization of Cell Adhesion by JNK Signaling

作者：Bornstein Bavat; Zahavi Eitan Erez; Gelley Sivan; Zoosman Maayan; Yaniv Shiri Penina; Fuchs Ora; Porat Ziv; Perlson Eran; Schuldiner Oren^*

来源：Neuron, 2015, 88(5): 926-940.

DOI：10.1016/j.neuron.2015.10.023

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 gamma 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.

• 出版日期2015-12-2