Pilkinton M et al. (2007) Oncogene "Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex."

Sandoval R, Pilkinton M, Colamonici OR

[Oncogene, 2007]

Mammalian Mip/LIN-9 is a cell cycle regulatory protein that is negatively regulated by CDK4/cyclin D. It has been demonstrated that Mip/LIN-9 collaborates with B-Myb during S and G(2)/M in the induction of cyclins A and B, and CDK1. The ortholog of Mip/LIN-9 in Drosophila, Mip130, is part of a large multisubunit protein complex that includes RBF, repressor E2Fs and Myb, in what was termed the dREAM complex. A similar complex, although lacking B-Myb, was also described in Caenorhabditis elegans. Here, we demonstrate that unlike Drosophila, Mip/LIN-9 has mutually exclusive and cell cycle-phase-specific interactions with the mammalian orthologs of the dREAM complex. In G(0)/early G(1), Mip/LIN-9 forms a complex with E2F4 and p107 or p130, while in late G(1)/S phase, it associates with B-Myb. The separation of Mip/LIN-9 from p107,p130/E2F4 is likely driven by phosphorylation of the pocket proteins by CDK4 since Mip/LIN-9 fails to interact with phosphorylated forms of p107,p130. Importantly, the repressor complex that Mip/LIN-9 forms with p107 takes functional precedence over the transcriptional activation linked to the Mip/LIN-9 and B-Myb interaction since expression of p107 blocks the activation of the cyclin B promoter triggered by B-Myb and Mip/LIN-9.Oncogene advance online publication, 11 June 2007; doi:10.1038/sj.onc.1210562.

Olivier Zugasti et al. (2008) C.elegans Aging, Stress, Pathogenesis, and Heterochrony Meeting "Neuroimmune regulation of antimicrobial peptide expression via a non-canonical TGF-beta signalling pathway in C. elegans"

Olivier Zugasti, Jonathan Ewbank, Leopold Kurz

[C.elegans Aging, Stress, Pathogenesis, and Heterochrony Meeting, 2008]

Following sterile injury or infection by the fungal pathogen Drechmeria coniospora, betabetabeta

Schlotterer A et al. (2009) Diabetes "C. elegans as model for the study of high glucose- mediated life span reduction."

Bozorgmehr F, Schwenger V, Thornalley P, Hamann A, Brownlee M, Stern D, Hutter H, Zeier M, Kukudov G, Schlotterer A, Morcos M, Bierhaus A, Ibrahim Y, Oikonomou D, Fleming T, Pfisterer F, Du X, Rabbani N, Nawroth P, Sayed A, Humpert P

[Diabetes, 2009]

OBJECTIVE: Establishing Caenorhabditis elegans as a model for glucose toxicity-mediated life span reduction. RESEARCH DESIGN AND METHODS: C. elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high glucose on life span, glyoxalase-1 activity, advanced glycation end products (AGEs), and reactive oxygen species (ROS) formation and on mitochondrial function were studied. RESULTS: High glucose conditions reduced mean life span from 18.5 + or - 0.4 to 16.5 + or - 0.6 days and maximum life span from 25.9 + or - 0.4 to 23.2 + or - 0.4 days, independent of glucose effects on cuticle or bacterial metabolization of glucose. The formation of methylglyoxal-modified mitochondrial proteins and ROS was significantly increased by high glucose conditions and reduced by mitochondrial uncoupling and complex IIIQo inhibition. Overexpression of the methylglyoxal-detoxifying enzyme glyoxalase-1 attenuated the life-shortening effect of glucose by reducing AGE accumulation (by 65%) and ROS formation (by 50%) and restored mean (16.5 + or - 0.6 to 20.6 + or - 0.4 days) and maximum life span (23.2 + or - 0.4 to 27.7 + or - 2.3 days). In contrast, inhibition of glyoxalase-1 by RNAi further reduced mean (16.5 + or - 0.6 to 13.9 + or - 0.7 days) and maximum life span (23.2 + or - 0.4 to 20.3 + or - 1.1 days). The life span reduction by glyoxalase-1 inhibition was independent from the insulin signaling pathway because high glucose conditions also affected daf-2 knockdown animals in a similar manner. CONCLUSIONS: C. elegans is a suitable model organism to study glucose toxicity, in which high glucose conditions limit the life span by increasing ROS formation and AGE modification of mitochondrial proteins in a daf-2 independent manner. Most importantly, glucose toxicity can be prevented by improving glyoxalase-1-dependent methylglyoxal detoxification or preventing mitochondrial dysfunction.

Rankin CH (2006) Curr Biol "Nematode behavior: the taste of success, the smell of danger!"

Rankin CH

[Curr Biol, 2006]

Through experience, the nematode worm Caenorhabditis elegans learns to distinguish high quality bacteria--food--from low quality or toxic bacteria. Increased release of the neurotransmitter serotonin onto identified interneurons determines whether C. elegans chooses to feed or leave.

Chan A et al. (2000) Worm Breeder's Gazette "Protocol for Antibody Staining Mitotic and Meiotic Chromosomes in the Gonad"

Chan A, Meyer BJ

[Worm Breeder's Gazette, 2000]

1. For any specific antibody try 1%, 1.5%, or 2% paraformaldehyde (PFA) with 5-minute fix:

Butcher SE et al. (2004) Nature Structural & Molecular Biology "STAR-studded circuitry."

Wickens M, Butcher SE

[Nature Structural & Molecular Biology, 2004]

A recent study reports the RNA sequences that bind to the translational repressor protein GLD-1. The data suggest that a network of developmental genes may be regulated by GLD-1 or related STAR proteins through silencing or alternative splicing.

Katschinski DM et al. (2003) Physiol Genomics "Hot worms can handle heavy metal. Focus on "HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans"."

Katschinski DM, Glueck SB

[Physiol Genomics, 2003]

Life developed in a stressful environment. Stressors at the cellular level include heat, hypoxia, oxidative or reductive substances, mechanical or osmotic pressure, and toxic compounds like heavy metals. Various molecular pathways, more or less specific for the different stressors, developed during evolution to combat the molecular consequences of cell stress. Thermal stress induces the induction of a highly conserved protein family, the heat shock proteins (HSP).

Longo VD et al. (2003) Science "Evolutionary medicine: from dwarf model systems to healthy centenarians?"

Finch CE, Longo VD

[Science, 2003]

Restriction of the number of calories consumed extends longevity in many organisms. In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation without irreversible side effects. In organisms ranging from yeast to mice, mutations in glucose or IGF-I-like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism. This information suggests a new category of drugs that could prevent or postpone diseases of aging with few adverse effects.

Rentsch D et al. (2024) Genetics "Tools and methods for cell ablation and cell inhibition in Caenorhabditis elegans."

Aoki I, Rentsch D, Bergs A, Gottschalk A, Elvers N, Seidenthal M, Shao J, Ruse C

[Genetics, 2024]

To understand the function of cells such as neurons within an organism, it can be instrumental to inhibit cellular function, or to remove the cell (type) from the organism, and thus to observe the consequences on organismic and/or circuit function and animal behavior. A range of approaches and tools were developed and used over the past few decades that act either constitutively or acutely and reversibly, in systemic or local fashion. These approaches make use of either drugs or genetically encoded tools. Also, there are acutely acting inhibitory tools that require an exogenous trigger like light. Here, we give an overview of such methods developed and used in the nematode Caenorhabditis elegans.

Derry WB (2023) FEBS J "Role of developmental pathways in disease."

Derry WB

[FEBS J, 2023]

Developmental programs are tightly regulated networks of molecular and cellular signaling pathways that orchestrate the formation and organization of tissues and organs during organismal development. However, these programs can be disrupted or activated in an untimely manner, or in the wrong tissues, and this can lead to a host of diseases. This aberrant re-activation can occur due to a multitude of factors, including genetic mutations, environmental influences, or epigenetic modifications. Consequently, cells may undergo abnormal growth, differentiation, or migration, leading to structural abnormalities or functional impairments at the tissue or organismal level. This Subject Collection of The FEBS Journal on Developmental Pathways in Disease highlights 11 reviews and three research articles that cover a broad array of topics focused on the role of signaling pathways critical for normal development that are deregulated in human disease.