A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in<i>C. elegans</i>

Weicksel, Steven E.; Mahadav, Assaf; Moyle, Mark W.; Cipriani, Patricia Giselle; Kudron, Michelle M.; Pincus, Zachary; Bahmanyar, Shirin; Abriola, Laura; Merkel, Janie; Gutwein, Michelle; Fernandez, Anita; Piano, Fabio; Gunsalus, Kristin C.; Reinke, V

doi:10.1242/dev.140046

Cited by 15 publications

(11 citation statements)

References 34 publications

(37 reference statements)

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“…As above, supplemental cholesterol is necessary in our system. Perhaps related, we have found that the compound C22, which produces 100% sterility in standard agar plates, 53 has more variable effects in our corral system.…”

Section: Discussionmentioning

confidence: 64%

A simple culture system for long-term imaging of individual C. elegans

et al. 2017

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We have miniaturized standard culture techniques to rear arrays of isolated, individual C. elegans throughout their lives on solid gel media. The resulting apparatus is compatible with brightfield and fluorescent microscopy, enabling longitudinal studies of morphology and fluorescent transgene expression. Our culture system exploits a novel crosslinking reaction between a polyethylene glycol hydrogel and a silicone elastomer to constrain animals to individual “corrals” on the gel surface. These devices are simple to construct on the benchtop with commercially available reagents, and, unlike microfluidic isolation methods, does not rely on micropatterned materials. We demonstrate that this new culture method has negligible effects on the physiology of C. elegans compared to standard culture on agar plates. In addition, RNAi techniques are effective in this system. Finally, the hydrogel–silicone binding chemistry that we developed also allows traditional microfluidic devices to be covalently attached to gel substrates instead of glass.

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Section: Discussionmentioning

confidence: 64%

A simple culture system for long-term imaging of individual C. elegans

et al. 2017

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“…Comparisons between the embryonic lethality caused by ZTDO and another embryocide reveal key differences in mode of action. In C. elegans, C22 is a potent and species-specific embryocide that disrupts the oocyte-to-embryo transition in the maternal environment (Weicksel et al, 2016). C22 acts only through the parental hermaphrodites and targets oocytes just prior to fertilization, but has no effect on any other developmental stages, such as embryos, larvae and adults.…”

Section: Discussionmentioning

confidence: 99%

A species-specific nematocide that results in terminal embryogenesis

Renahan

Hong

2017

Journal of Experimental Biology

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Nematode-insect interactions are ubiquitous, complex and constantly changing as the host and nematode coevolve. The entomophilic nematode is found on a myriad beetle species worldwide, although the molecular dynamics of this relationship are largely unknown. To better understand how host cues affect embryogenesis, we characterized the threshold of sensitivity to the pheromone ()-7-tetradecen-2-one (ZTDO) by determining the minimum exposure duration and developmental window that results in embryonic lethality. We found early-stage embryos exposed to volatile ZTDO for as few as 4 h all display terminal embryogenesis, characterized by punctuated development up to 48 h later, with abnormal morphology and limited cavity formation. To determine if the pheromone arrests pre-hatching development by suffocating or permeabilizing the eggshells, we raised embryos under anoxic conditions and also examined eggshell permeability using the lipophilic dye FM4-64. We found that asphyxiating the embryos arrested embryogenesis in a reversible manner but did not phenocopy the effects of ZTDO exposure, whereas the ZTDO-induced disruption of embryogenesis did correlate with increased eggshell permeability. The effects of ZTDO are also highly specific, as other lipid insect compounds do not produce any detectable embryocidal effect. The high specificity and unusual teratogenic effect of ZTDO may be important in mediating the host-nematode relationship by regulating development.

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“…CREB3 has been identified in regulating Golgi-stress and activation of ARF4 (Reiling et al 2013). A previous study in C. elegans links let-607 with the upregulation of sec-23 and other proteins involved in secretion (Weicksel et al 2016).…”

Section: Immunity Response Network Regulates Lipid Bilayer Stressmentioning

confidence: 98%

Combining Auxin-Induced Degradation and RNAi Screening Identifies Novel Genes Involved in Lipid Bilayer Stress Sensing in Caenorhabditis elegans

Venz¹,

Korosteleva²,

Jongsma³

et al. 2020

G3 Genes|Genomes|Genetics

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Alteration of the lipid composition of biological membranes interferes with their function and can cause tissue damage by triggering apoptosis. Upon lipid bilayer stress, the endoplasmic reticulum mounts a stress response similar to the unfolded protein response. However, only a few genes are known to regulate lipid bilayer stress. We performed a suppressor screen that combined the auxin-inducible degradation (AID) system with conventional RNAi in C. elegans to identify members of the lipid bilayer stress response. AID-mediated degradation of the mediator MDT-15, a protein required for the upregulation of fatty acid desaturases, induced the activation of lipid bilayer stress-sensitive reporters. We screened through most C. elegans kinases and transcription factors by feeding RNAi. We discovered nine genes that suppressed the lipid bilayer stress response in C. elegans. These suppressor genes included drl-1/MAP3K3, gsk-3/GSK3, let-607/CREB3, ire-1/IRE1, and skn-1/NRF1,2,3. Our candidate suppressor genes suggest a network of transcription factors and the integration of multiple tissues for a centralized lipotoxicity response in the intestine. Thus, we demonstrated proof-of-concept for combining AID and RNAi as a new screening strategy and identified eight conserved genes that had not previously been implicated in the lipid bilayer stress response.

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A novel small molecule that disrupts a key event during the oocyte-to-embryo transition inC. elegans

Cited by 15 publications

References 34 publications

A simple culture system for long-term imaging of individual C. elegans

A simple culture system for long-term imaging of individual C. elegans

A species-specific nematocide that results in terminal embryogenesis

Combining Auxin-Induced Degradation and RNAi Screening Identifies Novel Genes Involved in Lipid Bilayer Stress Sensing in Caenorhabditis elegans

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