Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans

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 gon...

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Main Authors:	Mor Levi-Ferber, Rewayd Shalash, Adrien Le-Thomas, Yehuda Salzberg, Maor Shurgi, Jennifer IC Benichou, Avi Ashkenazi, Sivan Henis-Korenblit
Format:	article
Language:	EN
Published:	eLife Sciences Publications Ltd 2021
Subjects:	ER stress pluripotency RIDD teratoma germline neuronal circuit Medicine R Science Q Biology (General) QH301-705.5
Online Access:	https://doaj.org/article/774bac0ce2bc43779926e170e459fba1
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spelling	oai:doaj.org-article:774bac0ce2bc43779926e170e459fba12021-11-17T10:50:59ZNeuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans10.7554/eLife.656442050-084Xe65644https://doaj.org/article/774bac0ce2bc43779926e170e459fba12021-09-01T00:00:00Zhttps://elifesciences.org/articles/65644https://doaj.org/toc/2050-084XUnderstanding 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.Mor Levi-FerberRewayd ShalashAdrien Le-ThomasYehuda SalzbergMaor ShurgiJennifer IC BenichouAvi AshkenaziSivan Henis-KorenbliteLife Sciences Publications LtdarticleER stresspluripotencyRIDDteratomagermlineneuronal circuitMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ER stress pluripotency RIDD teratoma germline neuronal circuit Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	ER stress pluripotency RIDD teratoma germline neuronal circuit Medicine R Science Q Biology (General) QH301-705.5 Mor Levi-Ferber Rewayd Shalash Adrien Le-Thomas Yehuda Salzberg Maor Shurgi Jennifer IC Benichou Avi Ashkenazi Sivan Henis-Korenblit Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans
description	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.
format	article
author	Mor Levi-Ferber Rewayd Shalash Adrien Le-Thomas Yehuda Salzberg Maor Shurgi Jennifer IC Benichou Avi Ashkenazi Sivan Henis-Korenblit
author_facet	Mor Levi-Ferber Rewayd Shalash Adrien Le-Thomas Yehuda Salzberg Maor Shurgi Jennifer IC Benichou Avi Ashkenazi Sivan Henis-Korenblit
author_sort	Mor Levi-Ferber
title	Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans
title_short	Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans
title_full	Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans
title_fullStr	Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans
title_full_unstemmed	Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans
title_sort	neuronal regulated ire-1-dependent mrna decay controls germline differentiation in caenorhabditis elegans
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/774bac0ce2bc43779926e170e459fba1
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_version_	1718425618164482048

Neuronal regulated ire-1-dependent mRNA decay controls germline differentiation in Caenorhabditis elegans

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