title: Nitric Oxide as a Switching Mechanism between Axon Degeneration and Regrowth during Developmental Remodeling.
abstract: During development, neurons switch among growth states, such as initial axon outgrowth, axon pruning, and regrowth. By studying the stereotypic remodeling of the Drosophila mushroom body (MB), we found that the heme-binding nuclear receptor E75 is dispensable for initial axon outgrowth of MB γ neurons but is required for their developmental regrowth. Genetic experiments and pharmacological manipulations on ex-vivo-cultured brains indicate that neuronally generated nitric oxide (NO) promotes pruning but inhibits regrowth. We found that high NO levels inhibit the physical interaction between the E75 and UNF nuclear receptors, likely accounting for its repression of regrowth. Additionally, NO synthase (NOS) activity is downregulated at the onset of regrowth, at least partially, by short inhibitory NOS isoforms encoded within the NOS locus, indicating how NO production could be developmentally regulated. Taken together, these results suggest that NO signaling provides a switching mechanism between the degenerative and regenerative states of neuronal remodeling.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Rabinovich
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Shiri P
authors.initials: SP
authors.lastname: Yaniv
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Alyagor
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; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D024521:Mushroom Bodies; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C539176:Hr51 protein, Drosophila; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C061375:Eip75B protein, Drosophila; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase