scholarly journals AMPK Regulates Developmental Plasticity through an Endogenous Small RNA Pathway in Caenorhabditis elegans

2020 ◽  
Vol 21 (6) ◽  
pp. 2238
Author(s):  
Christopher Wong ◽  
Richard Roy
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Small Rna ◽  
Developmental Plasticity ◽  
Germ Line ◽  
Growth Conditions ◽  
Cell Integrity ◽  
Rna Biosynthesis ◽  
Amp Activated Protein Kinase ◽  
Dauer Larvae

Caenorhabditis elegans larvae can undergo developmental arrest upon entry into the dauer stage in response to suboptimal growth conditions. Dauer larvae can exit this stage in replete conditions with no reproductive consequence. During this diapause stage, the metabolic regulator AMP-activated protein kinase (AMPK) ensures that the germ line becomes quiescent to maintain germ cell integrity. Animals that lack all AMPK signalling undergo germline hyperplasia upon entering dauer, while those that recover from this stage become sterile. Neuronal AMPK expression in otherwise AMPK-deficient animals is sufficient for germline quiescence and germ cell integrity and its effects are likely mediated through an endogenous small RNA pathway. Upon impairing small RNA biosynthesis, the post-dauer fertility is restored in AMPK mutants. These data suggest that AMPK may function in neurons to relay a message through small RNAs to the germ cells to alter their quiescence in the dauer stage, thus challenging the permeability of the Weismann barrier.

scholarly journals AMPK regulates germline stem cell quiescence and integrity through an endogenous small RNA pathway

2018 ◽  
Author(s):  
Pratik Kadekar ◽  
Richard Roy
Keyword(s):  
Stem Cell ◽  
Germ Cell ◽  
Germ Cells ◽  
Small Rna ◽  
Germ Line ◽  
Negative Impact ◽  
Growth Conditions ◽  
Germline Stem Cell ◽  
Chromatin Modifications ◽  
Cell Integrity

AbstractC. elegans larvae can undergo a global developmental arrest following the execution of a diapause-like state called ‘dauer’ in response to unfavourable growth conditions. Survival in this stage surpasses the normal lifespan of reproductive animals quite dramatically, and without any apparent negative impact on their reproductive fitness. During this period, the germ cells become quiescent and must retain their reproductive integrity so the animal can reproduce following recovery. This germline stem cell (GSC) arrest requires the activity of AMP-activated protein kinase (AMPK) and in its absence the germ line undergoes hyperplasia. We show here that AMPK mutant animals exhibit complete sterility after recovery from dauer, suggesting that germ cell integrity is compromised during this stage in the absence of AMPK. These defects correlate with altered abundance and distribution of a number of chromatin modifications that affect gene expression. These aberrant chromatin modifications, along with the supernumerary germ cell divisions and the observed post-dauer sterility, were all corrected by disabling key effectors of the small interfering RNA pathway (dcr-1 and rde-4) and the primary Argonaute protein ergo-1, suggesting that AMPK regulates the function of these small RNA pathway components, and in its absence, the pathways become abnormally active. The aberrant regulation of the small RNA pathway components releases the germ cells from quiescence to proliferative state thereby compromising germ cell integrity. Curiously, AMPK expression in either the neurons or the excretory system is sufficient to restore the GSC quiescence and the fertility in the AMPK mutant post-dauer adults, while the fertility of these animals is also partially restored by disabling the dsRNA importer SID-1. Our data suggest that AMPK regulates a small RNA pathway in the soma to establish and/or maintain GSC quiescence and integrity cell non-autonomously in response to the energy stress associated with the dauer stage. Our findings therefore provide a unique model to better understand how the soma communicates with the germ line to establish the appropriate epigenetic modifications required to adapt to acute environmental challenges.

scholarly journals fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans.

Genetics ◽  
1990 ◽  
Vol 125 (1) ◽  
pp. 29-39 ◽  
Author(s):  
M K Barton ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Germ Line ◽  
Regulatory Gene ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Male Germ Line ◽  
Somatic Tissues ◽  
Lines Of Evidence

Abstract In wild-type Caenorhabditis elegans, the XO male germ line makes only sperm and the XX hermaphrodite germ line makes sperm and then oocytes. In contrast, the germ line of either a male or a hermaphrodite carrying a mutation of the fog-1 (feminization of the germ line) locus is sexually transformed: cells that would normally make sperm differentiate as oocytes. However, the somatic tissues of fog-1 mutants remain unaffected. All fog-1 alleles identified confer the same phenotype. The fog-1 mutations appear to reduce fog-1 function, indicating that the wild-type fog-1 product is required for specification of a germ cell as a spermatocyte. Two lines of evidence indicate that a germ cell is determined for sex at about the same time that it enters meiosis. These include the fog-1 temperature sensitive period, which coincides in each sex with first entry into meiosis, and the phenotype of a fog-1; glp-1 double mutant. Experiments with double mutants show that fog-1 is epistatic to mutations in all other sex-determining genes tested. These results lead to the conclusion that fog-1 acts at the same level as the fem genes at the end of the sex determination pathway to specify germ cells as sperm.

The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 561-577 ◽  
Author(s):  
R E Ellis ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Sexual Identity ◽  
Cell Fate ◽  
Germ Cells ◽  
Regulatory Network ◽  
Germ Line ◽  
The Other ◽  
Nematode Caenorhabditis Elegans ◽  
Inhibitory Interactions

Abstract In the nematode Caenorhabditis elegans, germ cells normally adopt one of three fates: mitosis, spermatogenesis or oogenesis. We have identified and characterized the gene fog-3, which is required for germ cells to differentiate as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3 is absolutely required for spermatogenesis and acts at the end of the regulatory hierarchy controlling sex determination for the germ line. By contrast, mutations in fog-3 do not alter the sexual identity of other tissues. We also have characterized the null phenotype of fog-1, another gene required for spermatogenesis; we demonstrate that it too controls the sexual identity of germ cells but not of other tissues. Finally, we have studied the interaction of these two fog genes with gld-1, a gene required for germ cells to undergo oogenesis rather than mitosis. On the basis of these results, we propose that germ-cell fate might be controlled by a set of inhibitory interactions among genes that specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a regulatory network would link the adoption of one germ-cell fate to the suppression of the other two.

scholarly journals The conserved phosphatase GSP-2/PP1 promotes germline immortality via small RNA-mediated genome silencing during meiosis

2018 ◽  
Author(s):  
Katherine Kretovich Billmyre ◽  
Anna-lisa Doebley ◽  
Bree Heestand ◽  
Tony Belicard ◽  
Aya Sato-Carlton ◽  
...  
Keyword(s):  
Germ Cell ◽  
Chromosome Segregation ◽  
Small Rna ◽  
Protein Phosphatase ◽  
Germ Line ◽  
Meiotic Chromosome ◽  
Loss Of Function ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Cell Immortality

AbstractGenomic silencing can promote germ cell immortality, or transgenerational maintenance of the germ line, via mechanisms that may occur during mitosis or meiosis. Here we report that the gsp-2 PP1/Glc7 phosphatase promotes germ cell immortality. We identified a separation-of-function allele of C. elegans GSP-2 that caused a meiosis-specific chromosome segregation defect and defects in transgenerational small RNA-induced genome silencing. GSP-2 is recruited to meiotic chromosomes by LAB-1, which also promoted germ cell immortality. Sterile gsp-2 and lab-1 mutant adults displayed germline degeneration, univalents and histone phosphorylation defects in oocytes, similar to small RNA genome silencing mutants. Epistasis and RNA analysis suggested that GSP-2 functions downstream of small RNAs. We conclude that a meiosis-specific function of GSP-2/LAB-1 ties small RNA-mediated silencing of the epigenome to germ cell immortality. Given that hemizygous genetic elements can drive transgenerational epigenomic silencing, and given that LAB-1 promotes pairing of homologous chromosomes and localizes to the interface between homologous chromosomes during pachytene, we suggest that discontinuities at this interface could promote nuclear silencing in a manner that depends on GSP-2.Author SummaryThe germ line of an organism is considered immortal in its capacity to give rise to an unlimited number of future generations. To protect the integrity of the germ line, mechanisms act to suppress the accumulation of transgenerational damage to the genome or epigenome. Loss of germ cell immortality can result from mutations that disrupt the small RNA-mediated silencing pathway that helps to protect the integrity of the epigenome. Here we report for the first time that the C. elegans protein phosphatase GSP-2 that promotes core chromosome biology functions during meiosis is also required for germ cell immortality. Specifically, we identified a partial loss of function allele of gsp-2 that exhibits defects in meiotic chromosome segregation and is also dysfunctional for transgenerational small RNA-mediated genome silencing. Our results are consistent with a known role of Drosophila Protein Phosphatase 1 in heterochromatin silencing, and point to a meiotic phosphatase function that is relevant to germ cell immortality, conceivably related to its roles in chromosome pairing or sister chromatid cohesion.

scholarly journals UHPLC-IM-Q-ToFMS analysis of maradolipids, found exclusively in Caenorhabditis elegans dauer larvae

2021 ◽  
Vol 413 (8) ◽  
pp. 2091-2102
Author(s):  
Michael Witting ◽  
Ulrike Schmidt ◽  
Hans-Joachim Knölker
Keyword(s):  
Caenorhabditis Elegans ◽  
Developmental Stage ◽  
Ion Mobility ◽  
Environmental Conditions ◽  
Multidimensional Data ◽  
Specific Class ◽  
Lipid Profiling ◽  
C Elegans ◽  
Tandem Mass Spectrometric ◽  
Dauer Larvae

AbstractLipid identification is one of the current bottlenecks in lipidomics and lipid profiling, especially for novel lipid classes, and requires multidimensional data for correct annotation. We used the combination of chromatographic and ion mobility separation together with data-independent acquisition (DIA) of tandem mass spectrometric data for the analysis of lipids in the biomedical model organism Caenorhabditis elegans. C. elegans reacts to harsh environmental conditions by interrupting its normal life cycle and entering an alternative developmental stage called dauer stage. Dauer larvae show distinct changes in metabolism and morphology to survive unfavorable environmental conditions and are able to survive for a long time without feeding. Only at this developmental stage, dauer larvae produce a specific class of glycolipids called maradolipids. We performed an analysis of maradolipids using ultrahigh performance liquid chromatography-ion mobility spectrometry-quadrupole-time of flight-mass spectrometry (UHPLC-IM-Q-ToFMS) using drift tube ion mobility to showcase how the integration of retention times, collisional cross sections, and DIA fragmentation data can be used for lipid identification. The obtained results show that combination of UHPLC and IM separation together with DIA represents a valuable tool for initial lipid identification. Using this analytical tool, a total of 45 marado- and lysomaradolipids have been putatively identified and 10 confirmed by authentic standards directly from C. elegans dauer larvae lipid extracts without the further need for further purification of glycolipids. Furthermore, we putatively identified two isomers of a lysomaradolipid not known so far. Graphical abstract

scholarly journals glp-3 Is Required for Mitosis and Meiosis in the Caenorhabditis elegans Germ Line

Genetics ◽  
1997 ◽  
Vol 145 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Lisa C Kadyk ◽  
Eric J Lambie ◽  
Judith Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cells ◽  
Germ Line ◽  
Stem Cell Population ◽  
Phenotypic Characterization ◽  
Loss Of Function ◽  
Dapi Staining ◽  
Cell Cycles ◽  
C Elegans ◽  
Mitosis And Meiosis

The germ line is the only tissue in Caenorhabditis elegans in which a stem cell population continues to divide mitotically throughout life; hence the cell cycles of the germ line and the soma are regulated differently. Here we report the genetic and phenotypic characterization of the glp-3 gene. In animals homozygous for each of five recessive loss-of-function alleles, germ cells in both hermaphrodites and males fail to progress through mitosis and meiosis, but somatic cells appear to divide normally. Germ cells in animals grown at 15° appear by DAPI staining to be uniformly arrested at the G2/M transition with <20 germ cells per gonad on average, suggesting a checkpoint-mediated arrest. In contrast, germ cells in mutant animals grown at 25° frequently proliferate slowly during adulthood, eventually forming small germ lines with several hundred germ cells. Nevertheless, cells in these small germ lines never undergo meiosis. Double mutant analysis with mutations in other genes affecting germ cell proliferation supports the idea that glp-3 may encode a gene product that is required for the mitotic and meiotic cell cycles in the C. elegans germ line.

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