C. elegansfeeding defective mutants have shorter body lengths and increased autophagy

Mörck, Catarina; Pilon, Marc

doi:10.1186/1471-213x-6-39

Cited by 149 publications

(66 citation statements)

References 46 publications

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“…The body length of the tax-6 mutant (795±71 µm) was about 70% of that of N2 (1126±77 µm), which is similar to the 60% change reported by Morck and Pilon [29], although their worm age (2 days after L4 larval stage) was different from ours (1 day after L4 larval stage).…”

Section: Resultssupporting

confidence: 85%

QuantWorm: A Comprehensive Software Package for Caenorhabditis elegans Phenotypic Assays

et al. 2014

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Phenotypic assays are crucial in genetics; however, traditional methods that rely on human observation are unsuitable for quantitative, large-scale experiments. Furthermore, there is an increasing need for comprehensive analyses of multiple phenotypes to provide multidimensional information. Here we developed an automated, high-throughput computer imaging system for quantifying multiple Caenorhabditis elegans phenotypes. Our imaging system is composed of a microscope equipped with a digital camera and a motorized stage connected to a computer running the QuantWorm software package. Currently, the software package contains one data acquisition module and four image analysis programs: WormLifespan, WormLocomotion, WormLength, and WormEgg. The data acquisition module collects images and videos. The WormLifespan software counts the number of moving worms by using two time-lapse images; the WormLocomotion software computes the velocity of moving worms; the WormLength software measures worm body size; and the WormEgg software counts the number of eggs. To evaluate the performance of our software, we compared the results of our software with manual measurements. We then demonstrated the application of the QuantWorm software in a drug assay and a genetic assay. Overall, the QuantWorm software provided accurate measurements at a high speed. Software source code, executable programs, and sample images are available at www.quantworm.org. Our software package has several advantages over current imaging systems for C. elegans. It is an all-in-one package for quantifying multiple phenotypes. The QuantWorm software is written in Java and its source code is freely available, so it does not require use of commercial software or libraries. It can be run on multiple platforms and easily customized to cope with new methods and requirements.

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Section: Resultssupporting

confidence: 85%

QuantWorm: A Comprehensive Software Package for Caenorhabditis elegans Phenotypic Assays

et al. 2014

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“…We also measured the lengths of worms developmentally matched at the L4 larval stage and found that wdr-23 L4 larval worms were 15% shorter than wild-type L4 worms (798.7 Ϯ 14.08 and 676.4 Ϯ 21.15 m for N2 and wdr-23 worms, respectively; P Ͻ 0.0001, n ϭ 12). Slow development and small body size can be caused by impaired feeding (35). However, the pharyngeal pumping rate of wdr-23 worms was not different from that of wild-type worms (124.7 Ϯ 4.31 and 127.8 Ϯ 2.19 pumps per minute for N2 and wdr-23 worms, respectively; P ϭ 0.58, n ϭ 20 to 30).…”

Section: Resultsmentioning

confidence: 92%

“…Here, we further characterized these worms to understand wdr-23 function in more detail. In C. elegans, small body size can be caused by slow larval development or a cuticle defect that results in a short and wide "dumpy" morphology (35). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

A Negative-Feedback Loop between the Detoxification/Antioxidant Response Factor SKN-1 and Its Repressor WDR-23 Matches Organism Needs with Environmental Conditions

Leung

Wang

Deonarine

et al. 2013

Molecular and Cellular Biology

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Negative-feedback loops between transcription factors and repressors in responses to xenobiotics, oxidants, heat, hypoxia, DNA damage, and infection have been described. Although common, the function of feedback is largely unstudied. Here, we define a negative-feedback loop between the Caenorhabditis elegans detoxification/antioxidant response factor SKN-1/Nrf and its repressor wdr-23 and investigate its function in vivo. Although SKN-1 promotes stress resistance and longevity, we find that tight regulation by WDR-23 is essential for growth and reproduction. By disabling SKN-1 transactivation of wdr-23, we reveal that feedback is required to set the balance between growth/reproduction and stress resistance/longevity. We also find that feedback is required to set the sensitivity of a core SKN-1 target gene to an electrophile. Interestingly, the effect of feedback on target gene induction is greatly reduced when the stress response is strongly activated, presumably to ensure maximum activation of cytoprotective genes during potentially fatal conditions. Our work provides a framework for understanding the function of negative feedback in inducible stress responses and demonstrates that manipulation of feedback alone can shift the balance of competing animal processes toward cell protection, health, and longevity. P rotective responses to cellular stress are coordinated by inducible transcription factors. Tight regulation of stress responses is essential, because they may have consequences for important processes such as growth, development, and reproduction. Negative feedback is a fundamental strategy for regulation of homeostatic processes at all levels of physiology. Simple two-component negative-feedback loops in which a transcription factor induces the expression of an interacting protein that represses the transcription factor are found within responses to diverse stressors, including DNA damage (1), oxidants (2), hypoxia (3), heat shock (4), and infection (5). Although the general importance of repression is recognized, the regulatory and physiological importance of feedback is unexplored.The Cap 'n' Collar (CNC) family of transcription factors orchestrates inducible antioxidant and detoxification responses in animal cells (6). CNC factors activate the expression of genes encoding enzymes that scavenge free radicals, synthesize glutathione, detoxify and export xenobiotics, and repair damage to proteins (6, 7). CNCs promote longevity in invertebrate models (8-11), and increased CNC activity is associated with long-lived and stress-resistant strains of mice (12). The main inducible CNC in humans is Nrf2, which is a popular chemopreventative target for diverse pathologies, including cancer, neurodegeneration, inflammation, asthma, and aging (13-16).Nrf2 is an unstable protein that is targeted for degradation by KEAP1, a Kelch repeat protein that functions as an adaptor for the CUL3 ubiquitin ligase. Oxidative modification of KEAP1 releases Nrf2 and allows it to accumulate and activate a cytoprotective gene expre...

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“…This suggests redundant roles for these factors during embryogenesis, likely outside of the seam cells. Possible functions of rnt-1 and bro-1 during embryogenesis are unknown at present, although it is intriguing that synthetic lethality between rnt-1 or bro-1 and a diverse collection of developmental genes have been reported, including dpy-22 (Xia et al, 2007), lon-1 (Ji et al, 2004), pha-2 and eat-3 (Mörck and Pilon, 2006). This suggests that bro-1 and rnt-1 may function in several different tissues in combination with other factors.…”

Section: Discussionmentioning

confidence: 99%

CEH-20/Pbx and UNC-62/Meis function upstream of rnt-1/Runx to regulate asymmetric divisions of the C. elegans stem-like seam cells

et al. 2013

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SummaryCaenorhabditis elegans seam cells divide in the stem-like mode throughout larval development, with the ability to both self-renew and produce daughters that differentiate. Seam cells typically divide asymmetrically, giving rise to an anterior daughter that fuses with the hypodermis and a posterior daughter that proliferates further. Previously we have identified rnt-1 (a homologue of the mammalian cancer-associated stem cell regulator Runx) as being an important regulator of seam development, acting to promote proliferation; rnt-1 mutants have fewer seam cells whereas overexpressing rnt-1 causes seam cell hyperplasia. We isolated the interacting CEH-20/Pbx and UNC-62/Meis TALE-class transcription factors during a genome-wide RNAi screen for novel regulators of seam cell number. Animals lacking wild type CEH-20 or UNC-62 display seam cell hyperplasia, largely restricted to the anterior of the worm, whereas double mutants have many additional seam cells along the length of the animal. The cellular basis of the hyperplasia involves the symmetrisation of normally asymmetric seam cell divisions towards the proliferative stem-like fate. The hyperplasia is completely suppressed in rnt-1 mutants, and rnt-1 is upregulated in ceh-20 and unc-62 mutants, suggesting that CEH-20 and UNC-62 function upstream of rnt-1 to limit proliferative potential to the appropriate daughter cell. In further support of this we find that CEH-20 is asymmetrically localised in seam daughters following an asymmetric division, being predominantly restricted to anterior nuclei whose fate is to differentiate. Thus, ceh-20 and unc-62 encode crucial regulators of seam cell division asymmetry, acting via rnt-1 to regulate the balance between proliferation and differentiation.

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C. elegansfeeding defective mutants have shorter body lengths and increased autophagy

Abstract: Background: Mutations that cause feeding defects in the nematode C. elegans are known to increase life span. Here we show that feeding defective mutants also have a second general trait in common, namely that they are small.

Cited by 149 publications

References 46 publications

QuantWorm: A Comprehensive Software Package for Caenorhabditis elegans Phenotypic Assays

QuantWorm: A Comprehensive Software Package for Caenorhabditis elegans Phenotypic Assays

A Negative-Feedback Loop between the Detoxification/Antioxidant Response Factor SKN-1 and Its Repressor WDR-23 Matches Organism Needs with Environmental Conditions

CEH-20/Pbx and UNC-62/Meis function upstream of rnt-1/Runx to regulate asymmetric divisions of the C. elegans stem-like seam cells

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