title: It's all in your mind: determining germ cell fate by neuronal IRE-1 in C. elegans.
abstract: The C. elegans germline is pluripotent and mitotic, similar to self-renewing mammalian tissues. Apoptosis is triggered as part of the normal oogenesis program, and is increased in response to various stresses. Here, we examined the effect of endoplasmic reticulum (ER) stress on apoptosis in the C. elegans germline. We demonstrate that pharmacological or genetic induction of ER stress enhances germline apoptosis. This process is mediated by the ER stress response sensor IRE-1, but is independent of its canonical downstream target XBP-1. We further demonstrate that ire-1-dependent apoptosis in the germline requires both CEP-1/p53 and the same canonical apoptotic genes as DNA damage-induced germline apoptosis. Strikingly, we find that activation of ire-1, specifically in the ASI neurons, but not in germ cells, is sufficient to induce apoptosis in the germline. This implies that ER stress related germline apoptosis can be determined at the organism level, and is a result of active IRE-1 signaling in neurons. Altogether, our findings uncover ire-1 as a novel cell non-autonomous regulator of germ cell apoptosis, linking ER homeostasis in sensory neurons and germ cell fate.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Mor
authors.initials: M
authors.lastname: Levi-Ferber
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, New York, United States of America.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Salzberg
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Modi
authors.initials: M
authors.lastname: Safra
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Haviv-Chesner
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, New York, United States of America.
authors.forename: Hannes E
authors.initials: HE
authors.lastname: Bülow
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Henis-Korenblit
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D005854:Germ Cells / Q000254:growth & development; D006066:Gonads / Q000254:growth & development; D009474:Neurons / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C548541:XBP-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C541905:IRE-1 protein, C elegans