Neuronal IL-17 controls Caenorhabditis elegans developmental diapause through CEP-1/p53
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Abstract
During metazoan development, how cell division and metabolic programs are coordinated with nutrient availability remains unclear. Here, we show that nutrient availability signaled by the neuronal cytokine, ILC-17.1, switches Caenorhabditis elegans development between reproductive growth and dormancy by controlling the activity of the tumor suppressor p53 ortholog, CEP-1. Specifically, upon food availability, ILC-17.1 signaling by amphid neurons promotes glucose utilization and suppresses CEP-1/p53 to allow growth. In the absence of ILC-17.1, CEP-1/p53 is activated, up-regulates cell-cycle inhibitors, decreases phosphofructokinase and cytochrome C expression, and causes larvae to arrest as stress-resistant, quiescent dauers. We propose a model whereby ILC-17.1 signaling links nutrient availability and energy metabolism to cell cycle progression through CEP-1/p53. These studies describe ancestral functions of IL-17 s and the p53 family of proteins and are relevant to our understanding of neuroimmune mechanisms in cancer. They also reveal a DNA damage–independent function of CEP-1/p53 in invertebrate development and support the existence of a previously undescribed C. elegans dauer pathway.
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fgt-1
just in case it's at all useful, there is an mNG knockin available of fgt-1 at the CGC here: https://cgc.umn.edu/strain/NK2540
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suggesting there there may also occur a wider, albeit incomplete, dauer rescue in some tissues.
First, I just want to say that this is a really amazing body of work and I really enjoyed reading your pre-print!
I've thought a lot about quiescence / cell cycle entry / cell fate in the L3 reproductive system, and there might be some useful tools that could get you a tissue-specific, sensitive read-out of cell cycle entry. My former lab made some cell cycle sensors that change nuclear-->cytosolic localization from G0-->G1-->S-->G2 (this strain: https://cgc.umn.edu/strain/DQM543 from https://elifesciences.org/articles/63265) would be a sensitive marker of the change from G0 in the P cells to G1 if you had the right microscope.
It might be really interesting to look at this CDK activity sensor in situations where some tissues are in dauer …
suggesting there there may also occur a wider, albeit incomplete, dauer rescue in some tissues.
First, I just want to say that this is a really amazing body of work and I really enjoyed reading your pre-print!
I've thought a lot about quiescence / cell cycle entry / cell fate in the L3 reproductive system, and there might be some useful tools that could get you a tissue-specific, sensitive read-out of cell cycle entry. My former lab made some cell cycle sensors that change nuclear-->cytosolic localization from G0-->G1-->S-->G2 (this strain: https://cgc.umn.edu/strain/DQM543 from https://elifesciences.org/articles/63265) would be a sensitive marker of the change from G0 in the P cells to G1 if you had the right microscope.
It might be really interesting to look at this CDK activity sensor in situations where some tissues are in dauer and some are not!
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