title: A signaling network for patterning of neuronal connectivity in the Drosophila brain.
abstract: The precise number and pattern of axonal connections generated during brain development regulates animal behavior. Therefore, understanding how developmental signals interact to regulate axonal extension and retraction to achieve precise neuronal connectivity is a fundamental goal of neurobiology. We investigated this question in the developing adult brain of Drosophila and find that it is regulated by crosstalk between Wnt, fibroblast growth factor (FGF) receptor, and Jun N-terminal kinase (JNK) signaling, but independent of neuronal activity. The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF)-Breathless (FGF receptor) axon-retracting signal to modulate JNK activity. JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern.
authors.affiliation: Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven School of Medicine, Leuven, Belgium.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Srahna
authors.forename: Maarten
authors.initials: M
authors.lastname: Leyssen
authors.forename: Ching Man
authors.initials: CM
authors.lastname: Choi
authors.forename: Lee G
authors.initials: LG
authors.lastname: Fradkin
authors.forename: Jasprina N
authors.initials: JN
authors.lastname: Noordermeer
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Hassan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000502:physiology*; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes; D051153:Wnt Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C491438:Wnt5 protein, Drosophila; D048670:MAP Kinase Kinase 4; D020830:rac1 GTP-Binding Protein