RRC ID 75998
Author Levi-Ferber M, Shalash R, Le-Thomas A, Salzberg Y, Shurgi M, Benichou JI, Ashkenazi A, Henis-Korenblit S.
Title Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans.
Journal Elife
Abstract Understanding the molecular events that regulate cell pluripotency versus acquisition of differentiated somatic cell fate is fundamentally important. Studies in Caenorhabditis elegans demonstrate that knockout of the germline-specific translation repressor gld-1 causes germ cells within tumorous gonads to form germline-derived teratoma. Previously we demonstrated that endoplasmic reticulum (ER) stress enhances this phenotype to suppress germline tumor progression(Levi-Ferber et al., 2015). Here, we identify a neuronal circuit that non-autonomously suppresses germline differentiation and show that it communicates with the gonad via the neurotransmitter serotonin to limit somatic differentiation of the tumorous germline. ER stress controls this circuit through regulated inositol requiring enzyme-1 (IRE-1)-dependent mRNA decay of transcripts encoding the neuropeptide FLP-6. Depletion of FLP-6 disrupts the circuit's integrity and hence its ability to prevent somatic-fate acquisition by germline tumor cells. Our findings reveal mechanistically how ER stress enhances ectopic germline differentiation and demonstrate that regulated Ire1-dependent decay can affect animal physiology by controlling a specific neuronal circuit.
Volume 10
Published 2021-9-3
DOI 10.7554/eLife.65644
PII 65644
PMID 34477553
PMC PMC8416019
MeSH Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caspases Cell Differentiation / physiology* Endoplasmic Reticulum Stress / physiology Germ Cells / physiology* Gonads Neurons / physiology* Protein Serine-Threonine Kinases / metabolism RNA Stability
Resource
C.elegans tm351 tm2427 tm3023 tm1880 tm1888 tm1983 tm6109 tm2984 tm6232 tm10075