title: Axon regrowth during development and regeneration following injury share molecular mechanisms.
abstract: BACKGROUND
  The molecular mechanisms that determine axonal growth potential are poorly understood. Intrinsic growth potential decreases with age, and thus one strategy to identify molecular pathways controlling intrinsic growth potential is by studying developing young neurons. The programmed and stereotypic remodeling of Drosophila mushroom body (MB) neurons during metamorphosis offers a unique opportunity to uncover such mechanisms. Despite emerging insights into MB γ-neuron axon pruning, nothing is known about the ensuing axon re-extension.
  
  
  RESULTS
  Using mosaic loss of function, we found that the nuclear receptor UNF (Nr2e3) is cell autonomously required for the re-extension of MB γ-axons following pruning, but not for the initial growth or guidance of any MB neuron type. We found that UNF promotes this process of developmental axon regrowth via the TOR pathway as well as a late axon guidance program via an unknown mechanism. We have thus uncovered a novel developmental program of axon regrowth that is cell autonomously regulated by the UNF nuclear receptor and the TOR pathway.
  
  
  CONCLUSIONS
  Our results suggest that UNF activates neuronal re-extension during development. Taken together, we show that axon growth during developmental remodeling is mechanistically distinct from initial axon outgrowth. Due to the involvement of the TOR pathway in axon regeneration following injury, our results also suggests that developmental regrowth shares common molecular mechanisms with regeneration following injury.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shiri P
authors.initials: SP
authors.lastname: Yaniv
authors.forename: Noa
authors.initials: N
authors.lastname: Issman-Zecharya
authors.forename: Meital
authors.initials: M
authors.lastname: Oren-Suissa
authors.forename: Benjamin
authors.initials: B
authors.lastname: Podbilewicz
authors.forename: Oren
authors.initials: O
authors.lastname: Schuldiner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D008675:Metamorphosis, Biological / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024521:Mushroom Bodies / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D000076205:Ras Homolog Enriched in Brain Protein; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C539176:Hr51 protein, Drosophila; D009479:Neuropeptides; D000076205:Ras Homolog Enriched in Brain Protein; D018160:Receptors, Cytoplasmic and Nuclear; C490212:Rheb protein, Drosophila; C515347:TSC1 protein, Drosophila; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins