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[
Science,
2005]
After anaphase onset, animal cells build an actomyosin contractile ring that constricts the plasma membrane to generate two daughter cells connected by a cytoplasmic bridge. The bridge is ultimately severed to complete cytokinesis. Myriad techniques have been used to identify proteins that participate in cytokinesis in vertebrates, insects, and nematodes. A conserved core of about 20 proteins are individually involved with cytokinesis in most animal cells. These components are found in the contractile ring, on the central spindle, within the RhoA pathway, and on vesicles that expand the membrane and sever the bridge. Cytokinesis involves additional proteins, but they, or their requirement in cytokinesis, are not conserved among animal cells.
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[
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
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[
Curr Opin Genet Dev,
1994]
A receptor tyrosine kinase/Ras signaling pathway controls the specification of vulval cell fates in Caenorhabditis elegans. Recently, C. elegans genes encoding proteins with similarity to mammalian Raf (
lin-45), mitogen-activated protein kinase (
mpk-1/sur-1), and an HNF-3 transcription factor (
lin-31) have been identified and shown to act downstream of
let-60 (ras) in this pathway. These genetically identified gene products bridge the gap between signal transduction at the plasma membrane and the control of cell fate specification in the nucleus.
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ACS Chem Biol,
2007]
Invertebrate animal models (mainly the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster) are gaining momentum as screening tools in drug discovery. These organisms combine genetic amenability, low cost, and culture conditions compatible with large-scale screens. Their main advantage is to allow high-throughput screening in a physiological context. On the down side, protein divergence between invertebrates and humans causes a high rate of false negatives. Despite important limitations, invertebrate models are an imperfect yet much needed tool to bridge the gap between traditional in vitro and preclinical animal assays.
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[
Cell Microbiol,
2018]
Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-B, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.
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[
WormBook,
2006]
The architecture and dynamics of molecular networks can provide an understanding of complex biological processes complementary to that obtained from the in-depth study of single genes and proteins. With a completely sequenced and well-annotated genome, a fully characterized cell lineage, and powerful tools available to dissect development, Caenorhabditis elegans, among metazoans, provides an optimal system to bridge cellular and organismal biology with the global properties of macromolecular networks. This chapter considers omic technologies available for C. elegans to describe molecular networks - encompassing transcriptional and phenotypic profiling as well as physical interaction mapping - and discusses how their individual and integrated applications are paving the way for a network-level understanding of C. elegans biology.
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[
Front Cell Dev Biol,
2022]
The canonical eukaryotic cell cycle ends with cytokinesis, which physically divides the mother cell in two and allows the cycle to resume in the newly individualized daughter cells. However, during germline development in nearly all metazoans, dividing germ cells undergo incomplete cytokinesis and germ cells stay connected by intercellular bridges which allow the exchange of cytoplasm and organelles between cells. The near ubiquity of incomplete cytokinesis in animal germ lines suggests that this is an ancient feature that is fundamental for the development and function of this tissue. While cytokinesis has been studied for several decades, the mechanisms that enable regulated incomplete cytokinesis in germ cells are only beginning to emerge. Here we review the current knowledge on the regulation of germ cell intercellular bridge formation, focusing on findings made using mouse, Drosophila melanogaster and Caenorhabditis elegans as experimental systems.
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[
Cells,
2024]
Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of <i>C. elegans</i> models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of the <i>C. elegans</i> system in the realm of ALS research and point towards future investigations that could bridge the chasm between <i>C. elegans</i> foundational discoveries and clinical applications.
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[
Cell Microbiol,
2018]
Motile cells and pathogens migrate in complex environments and yet are mostly studied on simple 2D substrates. In order to mimic the diverse environments of motile cells a set of assays including substrates of defined elasticity, microfluidics, micropatterns, organotypic cultures and 3D gels have been developed. We briefly introduce these and then focus on the use of micro-patterned pillar arrays, which help to bridge the gap between 2D and 3D. These structures are made from polydimethylsiloxane, a moldable plastic and their use has revealed new insights into mechanoperception in Caenorhabditis elegans, gliding motility of Plasmodium, swimming of trypanosomes and nuclear stability in cancer cells. These studies contributed to our understanding of how the environment influences the respective cell and inform on how the cells adapt to their natural surroundings on a cellular and molecular level.
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[
Semin Cell Dev Biol,
2021]
Development of a syncytial germline for gamete formation requires complex regulation of cytokinesis and cytoplasmic remodeling. Recently, several uncovered cellular events have been investigated in the Caenorhabditis elegans (C. elegans) germline. In these cellular processes, the factors involved in contractility are highly conserved with those of mitosis and meiosis. However, the underlying regulatory mechanisms are far more complicated than previously thought, likely due to the single syncytial germline structure. In this review, we highlight how the proteins involved in contractility ensure faithful cell division in different cellular contexts and how they contribute to maintaining intercellular bridge stability. In addition, we discuss the current understanding of the cellular events of cytokinesis and cytoplasmic remodeling during the development of the C. elegans germline, including progenitor germ cells, germ cells, and spermatocytes. Comparisons are made with relevant systems in Drosophila melanogaster (D. melanogaster) and other animal models.