title: Developmental Axon Pruning Requires Destabilization of Cell Adhesion by JNK Signaling.
abstract: 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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Bavat
authors.initials: B
authors.lastname: Bornstein
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eitan Erez
authors.initials: EE
authors.lastname: Zahavi
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Gelley
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Zoosman
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Shiri Penina
authors.initials: SP
authors.lastname: Yaniv
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Ora
authors.initials: O
authors.lastname: Fuchs
authors.affiliation: Flow Cytometry Unit, Biological Services Department, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Perlson
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel. Electronic address: oren.schuldiner@weizmann.ac.il.
authors.forename: Oren
authors.initials: O
authors.lastname: Schuldiner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002448:Cell Adhesion / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008856:Microscopy, Fluorescence; D024521:Mushroom Bodies / Q000166:cytology* / Q000254:growth & development*; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D036123:Receptor, EphA5 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C051642:fasciclin II; D049452:Green Fluorescent Proteins; D036123:Receptor, EphA5