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Genetics,
2023]
The studies of cell fate and lineage specification are fundamental to our understanding of the development of multicellular organisms. Caenorhabditis elegans has been one of the premiere systems for studying cell fate specification mechanisms at single cell resolution, due to its transparent nature, the invariant cell lineage, and fixed number of somatic cells. We discuss the general themes and regulatory mechanisms that have emerged from these studies, with a focus on somatic lineages and cell fates. We next review the key factors and pathways that regulate the specification of discrete cells and lineages during embryogenesis and postembryonic development; we focus on transcription factors and include numerous lineage diagrams that depict the expression of key factors that specify embryonic founder cells and postembryonic blast cells, and the diverse somatic cell fates they generate. We end by discussing some future perspectives in cell and lineage specification.
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J Cell Biochem,
2013]
microRNA (miRNA) is a family of small, non-coding RNA first discovered as an important regulator of development in Caenorhabditis elegans (C. elegans). Numerous miRNAs have been found in C. elegans, and some of them are well conserved in many organisms. Though, the biologic function of miRNAs in C. elegans was largely unknown, more and more studies support the idea that miRNA is an important molecular for C. elegans. In this review, we revisit the research progress of miRNAs in C. elegans related with development, aging, cancer, and neurodegenerative diseases and compared the function of miRNAs between C. elegans and human.
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Methods,
2015]
PTEN (phosphatase and tensin homolog deleted on chromosome 10) has important roles in tumor suppression, metabolism, and development, yet its regulators, effectors, and functions are not fully understood. DAF-18 is the PTEN ortholog in Caenorhabditis elegans. DAF-18's role is highly conserved to human PTEN, and can be functionally replaced by human PTEN. Thus C. elegans provides a valuable model to study PTEN. This review assesses current and emerging methods to study DAF-18's regulators and functions in C. elegans. We propose genetic modify screens to identify genes that interact with
daf-18/PTEN. These genes are potential targets for anticancer drug therapies. We also provide a review on the roles DAF-18/PTEN has during C. elegans development and how studying these physiological roles can provide mechanistic insight on DAF-18/PTEN function.
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J Dev Biol,
2024]
As nervous systems mature, neural circuit connections are reorganized to optimize the performance of specific functions in adults. This reorganization of connections is achieved through a remarkably conserved phase of developmental circuit remodeling that engages neuron-intrinsic and neuron-extrinsic molecular mechanisms to establish mature circuitry. Abnormalities in circuit remodeling and maturation are broadly linked with a variety of neurodevelopmental disorders, including autism spectrum disorders and schizophrenia. Here, we aim to provide an overview of recent advances in our understanding of the molecular processes that govern neural circuit remodeling and maturation. In particular, we focus on intriguing mechanistic insights gained from invertebrate systems, such as the nematode <i>Caenorhabditis elegans</i> and the fruit fly <i>Drosophila melanogaster</i>. We discuss how transcriptional control mechanisms, synaptic activity, and glial engulfment shape specific aspects of circuit remodeling in worms and flies. Finally, we highlight mechanistic parallels across invertebrate and mammalian systems, and prospects for further advances in each.
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FEBS J,
2021]
Electron transport chain (ETC) dysfunction is a common feature of mitochondrial diseases and induces severe cellular stresses, including mitochondrial membrane potential (<sub>m</sub> ) reduction, mitochondrial matrix acidification, metabolic derangements and proteostatic stresses. Extensive studies of ETC dysfunction in yeast, C. elegans, cultured cells and mouse models have revealed multiple mitochondrial stress response pathways. Here, we summarize the current understanding of the triggers, sensors, signaling mechanisms, and the functional outcomes of mitochondrial stress responses in different species. We highlight <sub>m</sub> reduction as a major trigger of stress responses in different species, but the responses are species-specific and the outcomes are context-dependent. ETC dysfunction elicits a mitochondrial unfolded protein response (UPR<sup>mt</sup> ) to repair damaged mitochondria in C. elegans, and activates a global adaptive program to maintain <sub>m</sub> in yeast. Yeast and C. elegans responses are remarkably similar at the downstream responses, although they are activated by different signaling mechanisms. UPR<sup>mt</sup> generally protects ETC-defective worms, but its constitutive activation is toxic for wildtype worms and worms carrying mutant mtDNA. In contrast to lower organisms, ETC dysfunction in mammals mainly activates a mitochondrial integrated stress response (ISR<sup>mt</sup> ) to reprogram metabolism and a PINK1-Parkin mitophagy pathway to degrade damaged mitochondria. Accumulating in vivo results suggest that the ATF4 branch of ISR<sup>mt</sup> exacerbates metabolic derangements to accelerate mitochondrial disease progression. The in vivo roles of mitophagy in mitochondrial diseases are also context-dependent. These results thus reveal the common and unique aspects of mitochondrial stress responses in different species and highlight their multifaceted roles in mitochondrial diseases.
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Wiley Interdiscip Rev Dev Biol,
2012]
Myogenesis has proved to be a powerful paradigm for understanding cell fate specification and differentiation in many model organisms. Studies of somatic bodywall muscle (BWM) development in Caenorhabditis elegans allow us to define, with single cell resolution, the distinct hierarchies of transcriptional regulators needed for myogenesis throughout development. Although all 95 BWM cells appear uniform after differentiation, there are several different regulatory cascades employed embryonically and post-embryonically. These, in turn, are integrated into multiple extrinsic cell signaling events. The convergence of these different pathways on the key nodal point, that is the activation of the core muscle module, commits individual cells to myogenesis. Comparisons of myogenesis between C. elegans and other model systems provide insights into the evolution of contractile cell types, demonstrating the conservation of regulatory schemes for muscles throughout the animal kingdom.
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J Comp Physiol A Neuroethol Sens Neural Behav Physiol,
2015]
Temperature has profound effects on behavior and aging in both poikilotherms and homeotherms. To thrive under the ever fluctuating environmental temperatures, animals have evolved sophisticated mechanisms to sense and adapt to temperature changes. Animals sense temperature through various molecular thermosensors, such as thermosensitive transient receptor potential (TRP) channels expressed in neurons, keratinocytes, and intestine. These evolutionarily conserved thermosensitive TRP channels feature distinct activation thresholds, thereby covering a wide spectrum of ambient temperature. Temperature changes trigger complex thermosensory behaviors. Due to the simplicity of the nervous system in model organisms such as Caenorhabditis elegans and Drosophila, the mechanisms of thermosensory behaviors in these species have been extensively studied at the circuit and molecular levels. While much is known about temperature regulation of behavior, it remains largely unclear how temperature affects aging. Recent studies in C. elegans demonstrate that temperature modulation of longevity is not simply a passive thermodynamic phenomenon as suggested by the rate-of-living theory, but rather a process that is actively regulated by genes, including those encoding thermosensitive TRP channels. In this review, we discuss our current understanding of thermosensation and its role in aging.
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Philos Trans R Soc Lond B Biol Sci,
2016]
An item is chiral if it cannot be superimposed on its mirror image. Most biological molecules are chiral. The homochirality of amino acids ensures that proteins are chiral, which is essential for their functions. Chirality also occurs at the whole-cell level, which was first studied mostly in ciliates, single-celled protozoans. Ciliates show chirality in their cortical structures, which is not determined by genetics, but by 'cortical inheritance'. These studies suggested that molecular chirality directs whole-cell chirality. Intriguingly, chirality in cellular structures and functions is also found in metazoans. In Drosophila, intrinsic cell chirality is observed in various left-right (LR) asymmetric tissues, and appears to be responsible for their LR asymmetric morphogenesis. In other invertebrates, such as snails and Caenorhabditis elegans, blastomere chirality is responsible for subsequent LR asymmetric development. Various cultured cells of vertebrates also show intrinsic chirality in their cellular behaviours and intracellular structural dynamics. Thus, cell chirality may be a general property of eukaryotic cells. In Drosophila, cell chirality drives the LR asymmetric development of individual organs, without establishing the LR axis of the whole embryo. Considering that organ-intrinsic LR asymmetry is also reported in vertebrates, this mechanism may contribute to LR asymmetric development across phyla.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.
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Hermann, Editeurs des Sciences et des Arts. Paris, France.,
2002]
L'espce Caenorhabditis elegans fut dcrite en 1900 Alger par E. Maupas, qui s'intressait son mode de reproduction hermaphrodite. Plus tard, vers le milieu du vingtime sicle, V. Nigon et ses collaboratuers Lyon tudirent les reorganizations cellulaires accompagnant la fecundation et les premiers clivages. J. Brun isola les preiers mutants morpholgiques.