title: Novel DLK-independent neuronal regeneration in Caenorhabditis elegans shares links with activity-dependent ectopic outgrowth.
abstract: During development, a neuron transitions from a state of rapid growth to a stable morphology, and neurons within the adult mammalian CNS lose their ability to effectively regenerate in response to injury. Here, we identify a novel form of neuronal regeneration, which is remarkably independent of DLK-1/DLK, KGB-1/JNK, and other MAPK signaling factors known to mediate regeneration in Caenorhabditis elegans, Drosophila, and mammals. This DLK-independent regeneration in C. elegans has direct genetic and molecular links to a well-studied form of endogenous activity-dependent ectopic axon outgrowth in the same neuron type. Both neuron outgrowth types are triggered by physical lesion of the sensory dendrite or mutations disrupting sensory activity, calcium signaling, or genes that restrict outgrowth during neuronal maturation, such as SAX-1/NDR kinase or UNC-43/CaMKII. These connections suggest that ectopic outgrowth represents a powerful platform for gene discovery in neuronal regeneration. Moreover, we note numerous similarities between C. elegans DLK-independent regeneration and lesion conditioning, a phenomenon producing robust regeneration in the mammalian CNS. Both regeneration types are triggered by lesion of a sensory neurite via reduction of neuronal activity and enhanced by disrupting L-type calcium channels or elevating cAMP. Taken as a whole, our study unites disparate forms of neuronal outgrowth to uncover fresh molecular insights into activity-dependent control of the adult nervous system's intrinsic regenerative capacity.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118; Boston University Photonics Center, Boston, MA 02215;
authors.forename: Samuel H
authors.identifier: 0000-0003-2553-1396
authors.initials: SH
authors.lastname: Chung
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118; Boston University Photonics Center, Boston, MA 02215;
authors.forename: Mehraj R
authors.initials: MR
authors.lastname: Awal
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118; Boston University Photonics Center, Boston, MA 02215;
authors.forename: James
authors.initials: J
authors.lastname: Shay
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118; Boston University Photonics Center, Boston, MA 02215;
authors.forename: Melissa M
authors.initials: MM
authors.lastname: McLoed
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Department of Physics, Harvard University, Cambridge, MA 02138.
authors.forename: Eric
authors.initials: E
authors.lastname: Mazur
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118; Boston University Photonics Center, Boston, MA 02215; cvgabel@bu.edu.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Gabel
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D020746:Calcium Channels, L-Type; D009416:Nerve Regeneration
chemical_list: D029742:Caenorhabditis elegans Proteins; D020746:Calcium Channels, L-Type
keywords: DLK-1; activity-dependent ectopic axon outgrowth; axon regeneration; femtosecond laser ablation; lesion conditioning