Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans.
The molecular and cellular mechanisms that allow adult-stage neurons to regenerate following damage are poorly understood. Recently, axons of motoneurons and mechanosensory neurons in adult C. elegans were found to regrow after being snipped by femtosecond laser ablation. Here, we explore the molecular determinants of adult-stage axon regeneration using the AVM mechanosensory neurons. The first step in AVM axon development is a pioneer axonal projection from the cell body to the ventral nerve cord. We show that regeneration of the AVM axon to the ventral nerve cord lacks the deterministic precision of initial axon development, requiring competition and pruning of unwanted axon branches. Nevertheless, axons of injured AVM neurons regrow to the ventral nerve cord with over 60% reliability in adult animals. In addition, in contrast to initial development, axon guidance during regeneration becomes heavily dependent on cytoplasmic protein MIG-10/Lamellipodin but independent of UNC-129/TGF-beta repellent and UNC-40/DCC receptor, and axon growth during regeneration becomes heavily dependent on UNC-34/Ena and CED-10/Rac actin regulators. Thus, C. elegans may be used as a genetic system to characterize novel cellular and molecular mechanisms underlying adult-stage nervous system regeneration.
Gabel
Christopher V
CV
Department of Physics and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Antoine
Faustine
F
Antonie
Faustine
F
Chuang
Chiou-Fen
CF
Samuel
Aravinthan D T
AD
Chang
Chieh
C
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000502:physiology* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D017238:Genes, Helminth; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D009154:Mutation; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology
C407268:CED-10 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; C511070:unc-34 protein, C elegans; D020744:rac GTP-Binding Proteins