Askjaer P et al. (2014) WormBook "Modern techniques for the analysis of chromatin and nuclear organization in C. elegans."

Ercan S, Meister P, Askjaer P

[WormBook, 2014]

In recent years, Caenorhabditis elegans has emerged as a new model to investigate the relationships between nuclear architecture, cellular differentiation, and organismal development. On one hand, C. elegans with its fixed lineage and transparent body is a great model organism to observe gene functions in vivo in specific cell types using microscopy. On the other hand, two different techniques have been applied in nematodes to identify binding sites for chromatin-associated proteins genome-wide: chromatin immunoprecipitation (ChIP), and Dam-mediated identification (DamID). We summarize here all three techniques together as they are complementary. We also highlight strengths and differences of the individual approaches.

Conradt B (2000) Ernst Schering Res Found Workshop "Programmed cell death and its regulation and initiation in C. elegans."

Conradt B

[Ernst Schering Res Found Workshop, 2000]

The proliferation of cells is an integral part of development and tissue homeostatsis in multicellular animals(reviewed by Raff 1996; Folletee and O'farrel 1997). Two opposing processes, the division of cells on one hand and the programmed death of cells on the other hand, determine the overall rate of cell proliferation, The proper regulation of these two physiological processes is therefore a crucial aspect of development and of tissue homeostatsis(reviewed by Edgar and Lehner 1996; Shrr 1997;Jacobson et al. 1997). While the importance of the process of cell division has long been recognized, the role and extent of programmed cell death, or apoptosis, has only been realized within the last decades (Glucksmann 1950; Kerr et al. 19972). Massive programmed cell death occurs, for instance, during the development of the nervous system and in the immune system: more than 50% on all neurons and oligodendrocytes formed in the periperal and central vertebrate nervous system undergo programmed cell death neurogenesis...

Braendle C et al. (2009) J Biosci "The other side of phenotypic plasticity: a developmental system that generates an invariant phenotype despite environmental variation."

Felix MA, Braendle C

[J Biosci, 2009]

Understanding how the environment impacts development is of central interest in developmental and evolutionary biology. On the one hand, we would like to understand how the environment induces phenotypic changes (the study of phenotypic plasticity). On the other hand, we may ask how a development system maintains a stable and precise phenotypic output despite the presence of environmental variation. We study such developmental robustness to environmental variation using vulval cell fate patterning in the nematode Caenorhabditis elegans as a study system. Here we review both mechanistic and evolutionary aspects of these studies, focusing on recently obtained experimental results. First, we present evidence indicating that vulval formation is under stabilizing selection. Second, we discuss quantitative data on the precision and variability in the output of the vulval developmental system in different environments and different genetic backgrounds. Third, we illustrate how environmental and genetic variation modulate the cellular and molecular processes underlying the formation of the vulva. Fourth, we discuss the evolutionary significance of environmental sensitivity of this developmental system.

Straub T et al. (2011) Curr Opin Genet Dev "Transcription modulation chromosome-wide: universal features and principles of dosage compensation in worms and flies."

Straub T, Becker PB

[Curr Opin Genet Dev, 2011]

Dosage compensation processes in flies and worms provide a unique opportunity to study common regulatory principles of thousands of genes. Technological advancement in the recent years has allowed for the comprehensive description of key aspects such as the targeting of the regulatory factors, the emerging chromatin structure changes and the ensuing subtle transcriptional alterations. With plenty of data at hand the challenge remains to integrate the findings into coherent models that appreciate the global nature of the underlying principles leaving the experimental anecdotes behind while avoiding the numerical burlesque.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Klotz LO et al. (2015) Redox Biol "Redox regulation of FoxO transcription factors."

Monsalve M, Steinbrenner H, Klotz LO, Prieto-Arroyo I, Sanchez-Ramos C, Urbanek P

[Redox Biol, 2015]

Transcription factors of the forkhead box, class O (FoxO) family are important regulators of the cellular stress response and promote the cellular antioxidant defense. On one hand, FoxOs stimulate the transcription of genes coding for antioxidant proteins located in different subcellular compartments, such as in mitochondria (i.e. superoxide dismutase-2, peroxiredoxins 3 and 5) and peroxisomes (catalase), as well as for antioxidant proteins found extracellularly in plasma (e.g., selenoprotein P and ceruloplasmin). On the other hand, reactive oxygen species (ROS) as well as other stressful stimuli that elicit the formation of ROS, may modulate FoxO activity at multiple levels, including posttranslational modifications of FoxOs (such as phosphorylation and acetylation), interaction with coregulators, alterations in FoxO subcellular localization, protein synthesis and stability. Moreover, transcriptional and posttranscriptional control of the expression of genes coding for FoxOs is sensitive to ROS. Here, we review these aspects of FoxO biology focusing on redox regulation of FoxO signaling, and with emphasis on the interplay between ROS and FoxOs under various physiological and pathophysiological conditions. Of particular interest are the dual role played by FoxOs in cancer development and their key role in whole body nutrient homeostasis, modulating metabolic adaptations and/or disturbances in response to low vs. high nutrient intake. Examples discussed here include calorie restriction and starvation as well as adipogenesis, obesity and type 2 diabetes.

Sadeghian F et al. (2022) Life (Basel) "Functional Insights into Protein Kinase A (PKA) Signaling from C. elegans."

Castaneda PG, Sadeghian F, Cram EJ, Amin MR

[Life (Basel), 2022]

Protein kinase A (PKA), which regulates a diverse set of biological functions downstream of cyclic AMP (cAMP), is a tetramer consisting of two catalytic subunits (PKA-C) and two regulatory subunits (PKA-R). When cAMP binds the PKA-R subunits, the PKA-C subunits are released and interact with downstream effectors. In Caenorhabditis elegans (C. elegans), PKA-C and PKA-R are encoded by kin-1 and kin-2, respectively. This review focuses on the contributions of work in C. elegans to our understanding of the many roles of PKA, including contractility and oocyte maturation in the reproductive system, lipid metabolism, physiology, mitochondrial function and lifespan, and a wide variety of behaviors. C. elegans provides a powerful genetic platform for understanding how this kinase can regulate an astounding variety of physiological responses.

Schiavi A et al. (2014) Exp Gerontol "The interplay between mitochondria and autophagy and its role in the aging process."

Schiavi A, Ventura N

[Exp Gerontol, 2014]

Mitochondria are highly dynamic organelles which play a central role in cellular homeostasis. Mitochondrial dysfunction leads to life-threatening disorders and accelerates the aging process. Surprisingly, on the other hand, a mild reduction of mitochondria functionality can have pro-longevity effects in organisms spanning from yeast to mammals. Autophagy is a fundamental cellular housekeeping process that needs to be finely regulated for proper cell and organism survival, as underlined by the fact that both its over- and its defective activation have been associated with diseases and accelerated aging. A reciprocal interplay exists between mitochondria and autophagy, which is needed to constantly adjust cellular energy metabolism in different pathophysiological conditions. Here we review general features of mitochondrial function and autophagy with particular focus on their crosstalk and its possible implication in the aging process.

Westermann B (2010) Semin Cell Dev Biol "Mitochondrial dynamics in model organisms: what yeasts, worms and flies have taught us about fusion and fission of mitochondria."

Westermann B

[Semin Cell Dev Biol, 2010]

Mitochondrial fusion and fission are important for a great variety of cellular functions, including energy metabolism, development, aging and cell death. Many of the core components mediating mitochondrial dynamics in human cells have been first identified and mechanistically analyzed in model organisms, such as Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In particular, the functions of FZO/mitofusin and Mgm1/EAT-3/OPA1 in fusion and Dnm1/DRP1 in fission have been remarkably well conserved in yeasts, worms, flies and mammals. On the other hand, mechanisms to coordinate and regulate the activity of these molecular machines appear to be more diverse in different organisms. Here, I will discuss how S. cerevisiae, C. elegans and Drosophila have contributed to our current understanding of the cellular machineries mediating the dynamic behaviour of mitochondria.

Gleason RJ et al. (2022) Curr Opin Genet Dev "Epigenetic dynamics during germline development: insights from Drosophila and C. elegans."

Gleason RJ, Chen X

[Curr Opin Genet Dev, 2022]

Gametogenesis produces the only cell type within a metazoan that contributes both genetic and epigenetic information to the offspring. Extensive epigenetic dynamics are required to express or repress gene expression in a precise spatiotemporal manner. On the other hand, early embryos must be extensively reprogrammed as they begin a new life cycle, involving intergenerational epigenetic inheritance. Seminal work in both Drosophila and C. elegans has elucidated the role of various regulators of epigenetic inheritance, including (1) histones, (2) histone-modifying enzymes, and (3) small RNA-dependent epigenetic regulation in the maintenance of germline identity. This review highlights recent discoveries of epigenetic regulation during the stepwise changes of transcription and chromatin structure that takes place during germline stem cell self-renewal, maintenance of germline identity, and intergenerational epigenetic inheritance. Findings from these two species provide precedence and opportunity to extend relevant studies to vertebrates.