RRC ID 75918
Author Brar HK, Dey S, Bhardwaj S, Pande D, Singh P, Dey S, Ghosh-Roy A.
Title Dendrite regeneration in C. elegans is controlled by the RAC GTPase CED-10 and the RhoGEF TIAM-1.
Journal PLoS Genet
Abstract Neurons are vulnerable to physical insults, which compromise the integrity of both dendrites and axons. Although several molecular pathways of axon regeneration are identified, our knowledge of dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used the PVD neurons in C. elegans with stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After severing the primary dendrites near the cell body, we observed sprouting of new branches from the proximal site within 6 hours, which regrew further with time in an unstereotyped manner. This was accompanied by reconnection between the proximal and distal dendrites, and fusion among the higher-order branches as reported before. We quantified the regeneration pattern into three aspects-territory length, number of branches, and fusion phenomena. Axonal injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1 (DLK-1) dependent regrowth from the severed end. We tested the roles of the major axon regeneration signalling hubs such as DLK-1-RPM-1, cAMP elevation, let-7 miRNA, AKT-1, Phosphatidylserine (PS) exposure/PS in dendrite regeneration. We found that neither dendrite regrowth nor fusion was affected by the axon injury pathway molecules. Surprisingly, we found that the RAC GTPase, CED-10 and its upstream GEF, TIAM-1 play a cell-autonomous role in dendrite regeneration. Additionally, the function of CED-10 in epidermal cell is critical for post-dendrotomy fusion phenomena. This work describes a novel regulatory mechanism of dendrite regeneration and provides a framework for understanding the cellular mechanism of dendrite regeneration using PVD neuron as a model system.
Volume 18(3)
Pages e1010127
Published 2022-3-1
DOI 10.1371/journal.pgen.1010127
PII PGENETICS-D-21-01021
PMID 35344539
PMC PMC8989329
MeSH Animals Axons / metabolism Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Dendrites / metabolism GTP Phosphohydrolases / metabolism Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism MAP Kinase Kinase Kinases / genetics Nerve Regeneration / genetics Rho Guanine Nucleotide Exchange Factors / metabolism T-Lymphoma Invasion and Metastasis-inducing Protein 1* / metabolism rac GTP-Binding Proteins* / genetics rac GTP-Binding Proteins* / metabolism
Resource
C.elegans tm4024 tm469