title: Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila.
abstract: Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of neighboring postmitotic neurons during development regulates the robustness of axon target choice in a nondeterministic neuronal circuit. Specifically, neighboring postmitotic neurons communicate through Notch signaling during axonal targeting, to ensure balanced alternative axon target choices without a corresponding change in cell fate. Loss of Notch in postmitotic neurons modulates an axon's target choice. However, because neighboring axons respond by choosing the complementary target, the stereotyped connectivity pattern is preserved. In contrast, loss of Notch in clones of neighboring postmitotic neurons results in erroneous coinnervation by multiple axons. Our observations establish mutual inhibition of axonal target choice as a robustness mechanism for brain wiring and unveil a novel cell fate independent function for canonical Notch signaling. DOI:http://dx.doi.org/10.7554/eLife.00337.001.
authors.affiliation: Center for the Biology of Disease , VIB , Leuven , Belgium ; Center for Human Genetics , University of Leuven School of Medicine , Leuven , Belgium ; Doctoral Program in Molecular and Cognitive Neuroscience, Doctoral School of Biomedical Sciences , University of Leuven , Leuven , Belgium.
authors.forename: Marion
authors.initials: M
authors.lastname: Langen
authors.forename: Marta
authors.initials: M
authors.lastname: Koch
authors.forename: Jiekun
authors.initials: J
authors.lastname: Yan
authors.forename: Natalie
authors.initials: N
authors.lastname: De Geest
authors.forename: Maria-Luise
authors.initials: ML
authors.lastname: Erfurth
authors.forename: Barret D
authors.initials: BD
authors.lastname: Pfeiffer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmucker
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Hassan
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003198:Computer Simulation; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014795:Visual Pathways / Q000378:metabolism / Q000502:physiology*; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C099277:Pak protein, Drosophila; D054462:p21-Activated Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Axonal targeting; D. melanogaster; Neural Circuit; Neurobiology; Notch Signaling; Robustness; Variability