Pl3-kinase inhibition induces dauer formation, thermotolerance and longevity in C. elegans☆

The human genome encodes 10 insulin-like genes, whereas the Caenorhabditis elegans genome remarkably encodes 40 insulin-like genes. Knockout strategies to determine the roles of all the insulin/insulin-like peptide ligands (INS) in C. elegans has been challenging due to functional redundancy. Here, we individually overexpressed each of the 40 ins genes pan-neuronally, and monitored multiple phenotypes including: L1 arrest life span, neuroblast divisions under L1 arrest, dauer formation, and fat accumulation, as readouts to characterize the functions of each INS in vivo. Of the 40 INS peptides, we found functions for 35 INS peptides and functionally categorized each as agonists, antagonists, or of pleiotropic function. In particular, we found that 9 of 16 agonistic INS peptides shortened L1 arrest life span and promoted neuroblast divisions during L1 arrest. Our study revealed that a subset of β-class INS peptides that contain a distinct F peptide sequence are agonists. Our work is the first to categorize the structures of INS peptides and relate these structures to the functions of all 40 INS peptides in vivo. Our findings will promote the study of insulin function on development, metabolism, and aging-related diseases.

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Activation of hatching in diapaused and quiescent Globodera pallida

Parasitology ◽

10.1017/s0031182012001874 ◽

2012 ◽

Vol 140 (4) ◽

pp. 445-454 ◽

Cited By ~ 9

Author(s):

JUAN E. PALOMARES-RIUS ◽

JOHN T. JONES ◽

PETER J. COCK ◽

PABLO CASTILLO ◽

VIVIAN C. BLOK

Keyword(s):

Bursaphelenchus Xylophilus ◽

Globodera Pallida ◽

Parasitic Nematodes ◽

Plant Parasitic Nematodes ◽

Cyst Nematodes ◽

Term Survival ◽

C Elegans ◽

Dauer Formation ◽

Dorsal Gland

SUMMARYThe potato cyst nematodes (PCN) Globodera pallida and G. rostochiensis are major pests of potatoes. The G. pallida (and G. rostochiensis) life cycle includes both diapause and quiescent stages. Nematodes in dormancy (diapause or quiescent) are adapted for long-term survival and are more resistant to nematicides. This study analysed the mechanisms underlying diapause and quiescence. The effects of several compounds (8Br-cGMP, oxotremorine and atropine) on the activation of hatching were studied. The measurements of some morphometric parameters in diapaused and quiescent eggs after exposure to PRD revealed differences in dorsal gland length, subventral gland length and dorsal gland nucleolus. In addition, the expression of 2 effectors (IVg9 and cellulase) was not induced in diapaused eggs in water or PRD, while expression was slightly induced in quiescent eggs. Finally, we performed a comparative study to identify orthologues of C. elegans diapause related genes in plant-parasitic nematodes (G. pallida, Meloidogyne incognita, M. hapla and Bursaphelenchus xylophilus). This analysis suggested that it was not possible to identify G. pallida orthologues of the majority of C. elegans genes involved in the control of dauer formation. All these data suggest that G. pallida may use different mechanisms to C. elegans in regulating the survival stage.

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Identification of Ligands for DAF-12 that Govern Dauer Formation and Reproduction in C. elegans

Cell ◽

10.1016/j.cell.2006.01.037 ◽

2006 ◽

Vol 124 (6) ◽

pp. 1209-1223 ◽

Cited By ~ 270

Author(s):

Daniel L. Motola ◽

Carolyn L. Cummins ◽

Veerle Rottiers ◽

Kamalesh K. Sharma ◽

Tingting Li ◽

...

Keyword(s):

C Elegans ◽

Dauer Formation

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C. elegans dauer formation and the molecular basis of plasticity

Genes & Development ◽

10.1101/gad.1701508 ◽

2008 ◽

Vol 22 (16) ◽

pp. 2149-2165 ◽

Cited By ~ 315

Author(s):

N. Fielenbach ◽

A. Antebi

Keyword(s):

Molecular Basis ◽

C Elegans ◽

Dauer Formation

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Neuronal KGB-1 JNK MAPK signaling regulates the dauer developmental decision in response to environmental stress in C. elegans

10.1101/2021.06.28.450206 ◽

2021 ◽

Author(s):

Deepshikha Dogra ◽

Warakorn Kulalert ◽

Frank Schroeder ◽

Dennis H Kim

Keyword(s):

Elevated Temperature ◽

Signaling Pathways ◽

Mapk Pathway ◽

Negative Regulator ◽

Loss Of Function ◽

C Elegans ◽

Metabolic Remodeling ◽

Dauer Formation ◽

Identification And Characterization

In response to stressful growth conditions of high population density, food scarcity and elevated temperature, young larvae of nematode Caenorhabditis elegans can enter a developmentally arrested stage called dauer that is characterized by dramatic anatomic and metabolic remodeling. Genetic analysis of dauer formation of C. elegans has served as an experimental paradigm for the identification and characterization of conserved neuroendocrine signaling pathways. Here, we report the identification and characterization of a conserved JNK-like mitogen-activated protein kinase (MAPK) pathway that is required for dauer formation in response to environmental stressors. We observed that loss-of-function mutations in the MLK-1-MEK-1-KGB-1 MAPK pathway suppress dauer entry. Loss-of-function mutation in the VHP-1 MAPK phosphatase, a known negative regulator of KGB-1 signaling, results in constitutive dauer formation which is dependent on the presence of dauer pheromone but independent of diminished food levels or elevated temperatures. Our data suggest that KGB-1 pathway acts in the sensory neurons, in parallel to established insulin and TGF-β signaling pathways, to transduce the dauer-inducing environmental cues of diminished food levels and elevated temperature.

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Intergenerational pathogen-induced diapause in C. elegans is modulated by mir-243

10.1101/2020.03.31.019349 ◽

2020 ◽

Author(s):

Carolaing Gabaldon ◽

Marcela Legüe ◽

M. Fernanda Palominos ◽

Lidia Verdugo ◽

Florence Gutzwiller ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Developmental Change ◽

Differential Expression Analysis ◽

Phenotypic Analysis ◽

C Elegans ◽

Defensive Responses ◽

Animal Physiology ◽

Two Generations ◽

Dauer Formation ◽

And Behavior

AbstractThe interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNAi machinery, suggesting the involvement of sRNAs as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small non-coding RNAs, we found that mir-243-3p is the only transcript continuously upregulated in animals exposed to both, P. aeruginosa or S. enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small non-coding RNA in the intergenerational defensive response against pathogenic bacteria and inter-kingdom communication.ImportancePersistent infection of the bacterivore nematode C. elegans with bacteria such as P. aeruginosa and S. enterica makes the worm diapause or hibernate. By doing this, the worm closes its mouth avoiding infection. This response takes two generations to be implemented. In this work, we looked for genes expressed upon infection that could mediate the worm diapause triggered by pathogens. We identify mir-243-3p as the only transcript commonly upregulated when animals feed on P. aeruginosa and S. enterica for two consecutive generations. Moreover, we demonstrate that mir-243-3p is required for pathogen-induced dauer formation, a new function that has not been previously described for this miRNA. We also find that the transcriptional activators DAF-16, PQM-1 and CRH-2 are necessary for the expression of mir-243 under pathogenesis. Here we establish a relationship between a small RNA and a developmental change that ensures the survival of a percentage of the progeny.

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Intergenerational Pathogen-Induced Diapause in Caenorhabditis elegans Is Modulated by mir-243

mBio ◽

10.1128/mbio.01950-20 ◽

2020 ◽

Vol 11 (5) ◽

Author(s):

Carolaing Gabaldón ◽

Marcela Legüe ◽

M. Fernanda Palominos ◽

Lidia Verdugo ◽

Florence Gutzwiller ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Noncoding Rna ◽

Pathogenic Bacteria ◽

Developmental Change ◽

Differential Expression Analysis ◽

Phenotypic Analysis ◽

Content Type ◽

C Elegans ◽

Two Generations ◽

Dauer Formation

ABSTRACT The interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNA interference (RNAi) machinery, suggesting the involvement of small RNAs (sRNAs) as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small noncoding RNAs, we found that mir-243-3p (the mature form of mir-243) is the only transcript continuously upregulated in animals exposed to both Pseudomonas aeruginosa and Salmonella enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small noncoding RNA in the intergenerational defensive response against pathogenic bacteria and interkingdom communication. IMPORTANCE Persistent infection of the bacterivore nematode C. elegans with bacteria such as P. aeruginosa and S. enterica makes the worm diapause or hibernate. By doing this, the worm closes its mouth, avoiding infection. This response takes two generations to be implemented. In this work, we looked for genes expressed upon infection that could mediate the worm diapause triggered by pathogens. We identify mir-243-3p as the only transcript commonly upregulated when animals feed on P. aeruginosa and S. enterica for two consecutive generations. Moreover, we demonstrate that mir-243-3p is required for pathogen-induced dauer formation, a new function that has not been previously described for this microRNA (miRNA). We also find that the transcriptional activators DAF-16, PQM-1, and CRH-2 are necessary for the expression of mir-243 under pathogenesis. Here we establish a relationship between a small RNA and a developmental change that ensures the survival of a percentage of the progeny.

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