Mechanism Of Cell Division Research Articles

Mechanisms of asymmetric cell division during animal development

Recent years have seen the discovery of machineries for asymmetric cell division in a number of different organisms. The Inscuteable protein is a central component of such a machinery in Drosophila. Within dividing Drosophila neural precursor cells, Inscuteable directs both the orientation of the mitotic spindle and the asymmetric segregation of the proteins Numb, Prospero and Miranda into one of the two daughter cells. Numb can act by repressing signalling via the transmembrane receptor Notch, whereas Miranda localizes the transcription factor Prospero which initiates daughter cell specific gene expression. The identification of Numb homologs in other species has suggested that this machinery might be conserved from Drosophila to vertebrates.

Role of nutrition in the survival after hepatotoxic injury

Nutritional status is an important factor in determining susceptibility to toxic chemicals. While macro and micronutrients may affect many aspects of Stage I and Stage II of toxicity, in this paper, the influence of macronutrients as sources of energy required for cell division and tissue repair mechanisms on the outcome of hepatic injury is discussed. Male Sprague-Dawley rats maintained on normal rodent chow and 15% glucose (as a source of energy for the centrilobular hepatocytes) in drinking water for 7 days experienced an increased lethality from structurally and mechanistically different centrilobular hepatotoxicants (acetaminophen, thioacetamide, chloroform and carbon tetrachloride), while male Sprague-Dawley (S-D) rats fed rat chow containing palmitic acid (PA, 8% w/w, as a source of energy for the periportal hepatocytes) and l-carnitine (LC, 2 mg/ml, as a mitochondrial carrier for the supplemented fatty acids) in drinking water for 7 days were protected from a LD 100 dose (600 mg/kg, i.p.) of thioacetamide (TA). Indices of cell division revealed that cell cycle progression in the liver play a very critical role in determining the final outcome of hepatotoxic injury. These results confirmed our hypothesis that cell division and tissue repair play a critical role in survival after life-threatening hepatotoxic injury. Any manipulation directed towards altering a prompt and exacting compensatory cell division and tissue repair responses after hepatotoxic injury would also alter the final outcome of the toxicity. These studies indicate that the source of cellular energy can decisively influence the compensatory response of the target tissue to alter the outcome of hepatotoxic injury. Since nutritional status is known to vary widely among human populations, these could contribute enormously to susceptibility of human populations to toxic chemicals.

Collective oscillations in microtubule growth.

Large groups of microtubules are observed to undergo coherent oscillations in length. This process is suspected to be important to the mechanism of cell division. We propose a model, related to the bounded-unbounded transition of microtubules proposed by M. Dogterom and S. Leibler [Phys. Rev. Lett. 70, 1347 (1993)], which is in good agreement with experiments. \textcopyright{} 1996 The American Physical Society.

The mechanism of bacterial asymmetric cell division.

Asymmetric cell division generates two cells that contain different regulatory proteins and express different fates. In an example of asymmetric cell division from B. subtilis, a site on the membrane of the dividing cell is chosen to establish the initial asymmetry. Recent results show that a key regulatory protein, SpoIIE, is localized to one side of a sporulating B. subtilis cell, and subsequently functions in an asymmetric manner. SpoIIE is a phosphatase at the beginning of a regulatory cascade that leads to activation of a cell fate-determining transcription factor in only one daughter cell.

Involvement of active cellular mechanisms on the disorganization of oral apparatus in amicronucleate cells in Tetrahymena thermophila.

Ciliated protozoa, a group of unicellular eukaryotes, have two kinds of nuclei, a macronucleus (somatic nucleus) and a micronucleus (germinal nucleus) in a single cell. We previously reported that amicronucleate cells of Tetrahymena thermophila induced by nocodazole gradually lost their oral apparatus (OA) and ciliary rows but that amacronucleate cells did not. Since the macronucleus is responsible for the gene expression in the vegetative phase, the effects of actinomycin D and cycloheximide on the disorganization of the OA in amicronucleate cells induced by nocodazole were investigated. These inhibitors prevented the disorganization of the OA in amicronucleate cells. Amicronucleate cells did not grow even in the medium supplemented with high concentration of Fe, Cu and folinic acid which allow cells to grow without formation of food vacuoles. The results suggest that the macronucleus in the amicronucleate cells plays an active role in the induction of disorganization of the OA and malfunctions of nutrient uptake from the cell surface and/or in the fundamental cell division mechanisms, resulting in the death of amicronucleate cells.

A Deviating Pattern of Cell Division in the Green Alga Microthamnion: Ultrastructure of Vegetative Cell Division and Zoosporogenesis

Summary The ultrastructure of cell division of the green alga Microthamnion is described. It involves a unique mechanism for both vegetative cell division and zoosporogenesis. It starts with migration of the counterclockwise oriented centriole pair along the nuclear surface from the polar interphase position towards a lateral prophase position. The centriole pair duplicates and the root templates of the parental basal bodies grow out distally. Two microtubules of each of the two microtubular roots per basal body form two four-stranded microtubular bundles running along the cell wall and oriented perpendicular to the cell axis. At metaphase the separated centriole pairs have migrated to positions at approximately 180° from each other apparently via a sliding mechanism along the newly formed microtubular bundles. The microtubular bundles lie in the equatorial plane and curve over the nucleus, thus indicating the future division plane. In this respect the microtubular bundles resemble the preprophase band in higher plants. At anaphase the centriole pairs seem to have slightly co-migrated with the separating chromosome halves and thus the microtubular bundles show a shifted orientation with respect to the long axis of the cell. In this stage the unilateral septum starts to develop from the previous prophase position of the centriolar complex and progresses between the two four-stranded microtubular bundles. At telophase the daughter nuclei are reformed and the septum development proceeds. After cytokinesis the centrioles either return to the interphase position awaiting a new division cycle (vegetative cell division) or the centrioles take the prophase position in the newly formed daughter cells and duplicate in order to repeat the division cycle (zoosporogenesis). The ultrastructural features of Microthamnion are compared with the other pleurastrophycean algae and some chlamydomonadalean algae. However, the systematic position of Microthamnion still remains a matter of discussion.

Photoreceptor Apoptosis in Animal Models

In studyingthe life of cells, scientists have long focused their research on the essentially positive story of organisms' growth and self-maintenance. This story begins with cell division in embryos, progresses through the cell differentiation of early development, and arrives at the final stage of collective self-maintenance. Scientists have supplemented this story of cell growth with the discovery of different types of cell proliferation in the matured organism: that of the immune system, whereby antibody-producing cells will expand clonally to fight invaders of the organism, and that of cancer, whereby late reactivation of the otherwise healthy mechanisms of cell division and growth proceed uncontrollably, to the eventual detriment of the organism. For many years, then, scientists immersed themselves in narrowly defined problems posed by the various phenomena of cell proliferation. However, questions remained unanswered: How are excess cells disposed of during development? How are immune cells removed when they are no

Cell polarity and the mechanism of asymmetric cell division.

During development, one mechanism for generating different cell types is asymmetric cell division, by which a cell divides and contributes different factors to each of its daughter cells. Asymmetric cell division occurs throughout the eukaryotic kingdom, from yeast to humans. Many asymmetric cell divisions occur in a defined orientation. This implies a cellular mechanism for sensing direction, which must ultimately lead to differences in gene expression between two daughter cells. In this review, we describe two classes of molecules: regulatory factors that are differentially expressed upon asymmetric cell division, and components of a signal transduction pathway that may define cell polarity. The lin-11 and mec-3 genes of C. elegans, the Isl-1 gene of mammals and the HO gene of yeast, encode regulatory factors that determine cell type of one daughter after asymmetric cell division. The CDC24 and CDC42 genes of yeast affect both bud positioning and orientation of mating projections, and thus may define a general cellular polarity. We speculate that molecules such as Cdc24 and Cdc42 may regulate expression of genes such as lin-11, mec-3, Isl-1 and HO upon asymmetric cell division.

Inducing differentiation of transformed cells with hybrid polar compounds: a cell cycle-dependent process.

Transformed cells do not necessarily lose their capacity to differentiate. Various agents can induce many types of neoplastic cells to terminal differentiation. Among such inducers, a particularly potent group consists of hybrid polar compounds; hexamethylene bisacetamide (HMBA) is the prototype of this group. With virus-transformed murine erythroleukemia cells as a model, HMBA was shown to cause these cells to arrest in G1 phase and express globin genes. This review focuses on HMBA-induced modulation of factors regulating G1-to-S phase progression, including a decrease in the G1 cyclin-dependent kinase cdk4, associated with inhibition of phosphorylation of the retinoblastoma protein pRB and possibly other related proteins that, in turn, sequester factors required for initiation of DNA synthesis; this provides a possible mechanism for HMBA-induced terminal cell division. Evidence that hybrid polar compounds have therapeutic potential for cancer treatment will also be reviewed.

Cytoplasmic axial filaments in Escherichia coli cells: possible function in the mechanism of chromosome segregation and cell division.

Overproduction of CafA caused formation of chained cells and minicells. The cafA gene is located downstream from the mre region at 71 min on the Escherichia coli chromosome map and was previously called orfF. A long axial structure running through the chained cells, consisting of bundles of filaments assembled in a long hexagonal pillar several micrometers long and about 0.1 to 0.2 micron in diameter, was visible in both phase-contrast micrographs of the lysozyme-treated cells and electron micrographs of ultrathin sections. The CafA protein displays 34% amino acid similarity with the N terminus of the Ams protein of E. coli, which cross-reacts with antibody to a nonmuscle myosin heavy chain.

Escherichia coli cell division

Recent progress in the molecular analysis of bacterial septation and chromosome partitioning suggests that these processes may involve cytoskeletal elements previously thought to be present only in eukaryotic cells. The continued biochemical and genetic analysis of key proteins, such as the tubulin-like FtsZ, should lead to further unravelling of the regulation and mechanism of bacterial cell division.

A MODEL ON THE ORIGIN AND EVOLUTION OF DNA ANEUPLOIDY

A model on the origin and evolution of DNA aneuploidy based on a postulated mechanism of DNA asymmetrical cell division is presented. Asymmetry in cell division would be at the origin of hypodiploid cells in the near-diploid region. Tetraploidization of a hypodiploid cell would be one of the main routes by which advanced tumors may evolve to aneuploidy in the near-triploid region. The model is supported by nuclear DNA content data obtained by high resolution flow cytometry from fresh/frozen material during the colorectal tumor progression.

Functional analysis of the fic gene involved in regulation of cell division

We have shown that cAMP may be a regulation factor in cell division of Escherichia coli (Utsumi et al., 1982, 1989). The fic (filamentation induced by cAMP) gene of this system found previously (Utsumi, et al., 1982) was analysed in this study. The open reading frame of the fic gene coded for 200 amino acids. The pabA (p-aminobenzoate synthase) gene was found downstream from the fic gene. The distance between the end of fic and the start of pabA was 31 base pairs. To deduce the function of Fic protein, the fic gene was destroyed by the kanamycin-resistant (Km 1) gene and the fic gene was shown to be essential for growth of E. coli. Such mutants required PAB (p-aminobenzoate) or folate for growth. These data suggested that the Fic protein is involved in the synthesis of PAB or folate and the fic gene could be part of a pab operon. In cells starved of them, cell division was inhibited. Addition of folate also repressed the filamentation induced by cAMP at 43 °C in the fic-1 mutant. These results would indicate that Fic protein and cAMP are involved in a new regulatory mechanism of cell division via folate metabolism. Furthermore, it is also shown that cell division could be controlled by coordination of cAMP, Fic and Fts proteins.

Lonidamine: a non-mutagenic antitumor agent

Lonidiamine is a novel indazole-carboxylic acid with antitumour properties; it has been studied for potential mutagenicity in a comprehensive battery of tests. In assays for the induction of gene mutations in prokaryotes (Ames test) and eukaryotes (induction of HPRT mutations in CHO cells), negative results were obtained. There was no evidence of the induction of chromosomal damage in cultured mammalian cells in vitro. No mutagenic activity was observed in tests for chromosomal damage in vivo, in somatic cells (micronucleus test) or in germinal cells (dominant lethal test). These negative results are consistent with observations indicating that lonidamine affects cellular energy processes, rather than the mechanisms of cell division. The lack of mutagenic properties suggests that lonidamine may present significant advantages in treatment of some tumours, offering a reduced risk of resistant clones, secondary cancer and heritable genetic damage.

Identification of a gene that shortens clonal life span of Paramecium tetraurelia.

We have isolated a Paramecium tetraurelia mutant that divides slowly in daily reisolation cultures and repeats short clonal life spans after successive autogamies. Here we show, using breeding analysis, that a recessive mutation is responsible for the low fission rate and that this low rate is closely related to the short clonal life span. We conclude that a single pleiotropic gene controls these traits and have named it jumyo. In an attempt to further characterize the jumyo mutant, we have revealed that it has a culture life span similar to that of the wild-type cells and that, when mass cultured, it can divide as rapidly as wild-type cells. There was strong evidence that the mutant cells excreted into culture medium some substance that promotes their cell division. These findings may not only present supporting evidence for the hypothesis that the cellular life span is genetically programmed but also give a material basis for the study of the controlling mechanism of cell division in relation to the clonal life span.

Comparisons of tests for aneuploidy

The fundamental problems that face us in the development of suitable assay systems for the detection of potentially aneugenic (aneuploidy-inducing) chemicals include: (a) the diversity of cellular targets and mechanisms where perturbations of structure and function may give rise to changes in chromosome number, and (b) the phylogenetic differences that exist between species in their mechanism and kinetics of cell division and their metabolic profiles. A diverse range of assay systems have been developed, which have been shown to have potential for use in the detection of either changes in chromosome number or of perturbations of the events which may be causal in the induction of aneuploidy. Chromosome number changes may be detected cytologically by karyotypic analysis, or by the use of specialised strains in which aneuploid progeny may be observed due to phenotypic differences with aneuploid parental cells or whole organisms. Techniques for the detection of cellular target modifications range from in vitro studies of tubulin polymerisation to observations of the behaviour of various cellular organelles and their fidelity of action during the division cycle. The diversity of mechanisms which may give rise to aneuploidy and the qualitative relevance of events observed in experimental organisms compared to man make it unlikely that the detection and risk assessment of the aneugenic activity of chemicals will be possible using a single assay system. Optimal screening and assessment procedures will thus be dependent upon the selection of an appropriate battery of predictive tests for the measurement of the potentially damaging effects of aneuploidy induction.

Physiological Responses to Sethoxydim in Tissues of Corn (Zea mays) and Pea (Pisum sativum)

The physiological responses of corn (Zea maysL. ‘Goldencrossbantam′) and pea (Pisum sativumL. ‘Alaska′) to sethoxydim {2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio) propyl]-3-hydroxy-2-cyclohexen-1-one} were investigated. Sethoxydim did not affect excised pea root growth at 1 × 10−4M but inhibited excised corn root growth at concentrations of 1 × 10−8M and above. Treating corn impeded root growth with 1 × 10−7M sethoxydim within 4 h after treatment; however, little histological change of the roots was observed at 48 h. At 1 × 10−6M, growth nearly stopped within 4 h after treatment, and clear cytological changes of the roots were observed at 24 and 48 h. Sethoxydim inhibited both mitosis and DNA synthesis of excised corn root tips between 4 and 48 h after treatment. Respiration of corn roots measured by oxygen uptake and the TTC (2,3,5-triphenyltetrazolium chloride) test was not affected by the herbicide directly. Sethoxydim (1 × 10−4M) inhibited IAA-induced cell elongation of corn coleoptile and pea epicotyl by 37 and 12%, respectively. Sethoxydim selectively inhibited the growth of excised root tips of susceptible corn by affecting cell division rather than cell enlargement, and the inhibition mechanism of cell division (inhibition of mitosis) by the herbicide was not by direct inhibition of DNA synthesis or by effects on respiration.

Environmental control of cell morphology in desmids

The variability of the desmids was quite interesting to note that when the conditions such as temperature and illumination were altered, there was not only an increase in the abnormal forms but the number of the adherent cells were also more. This abnormal behaviour of the species was more or less directly proportionate to the altered status of these factors in culture. It was thus quite clear that due to an increase or decrease in temperature and light intensity, quite a number of variants were produced. Sometimes the cells departed so widely from the specific characteristic that one could mistake them as belonging to different taxa. It may be that under unfavourable conditions of growth the mechanism of cell division was disturbed lowering thereby the percentage of mitosis and finally leading to the tendency of morphological aberrations. Consequently, these observations induced to study the various species of desmids under different experimental conditions to find out the range of morphological variation in cultures because the feature which more than any other, has attracted algologists to study desmids especially placoderms is their considerable morphological variability. Morphological variations under different cultural conditions have been studied and it is presumed that the cell types are capable of maintaining their narrow specificity, which is genetically controlled under favourable conditions only, but, whenever, there is a change in environmental set-up, it has resulted in upsetting the metabolic behaviour leading to abnormal forms.

Promotion of Septation in Irradiated Escherichia coli by a Cytoplasmic Membrane Preparation

Septation can be promoted in an X-irradiated lon mutant of Escherichia coli K-12 by the addition of an E. coli B/r cytoplasmic membrane preparation to the postirradiation plating medium. The promotion of septation was not associated with an inhibition of growth rate. Two distinct cytoplasmic membrane-associated properties were necessary to promote septation. One of these, the cytochrome-based electron transport system, produced anaerobic conditions by the reduction of oxygen dissolved in the medium. The second system, functioning independently from the first, altered substances found in the peptone and yeast extract components of the postirradiation plating medium. When both systems were operative, significant repair of the cell division mechanism occurred.

Primeval cells: possible energy-generating and cell-division mechanisms.

It is proposed that the first entity capable of adaptive Darwinian evolution consisted of a liposome vesicle formed of abiotically produced phospholipidlike molecules; a very few informational macromolecules; and some abiogenic, lipid-soluble, organic molecule serving as a symporter for phosphate and protons and as a means of high-energy-bond generation. The genetic material had functions that led to the production of phospholipidlike materials (leading to growth and division of the primitive cells) and of the carrier needed for energy transduction. It is suggested that the most primitive exploitable energy source was the donation of 2H+ + 2e- at the external face of the primitive cell. The electrons were transferred (by metal impurities) to internal sinks of organic material, thus creating, via a deficit, a protonmotive force that could drive both the active transport of phosphate and high-energy-bond formation. This model implies that proton translocation in a closed-membrane system preceded photochemical or electron transport mechanisms and that chemically transferable metabolic energy was needed at a much earlier stage in the development of life than has usually been assumed. It provides a plausible mechanism whereby cell division of the earliest protocells could have been a spontaneous process powered by the internal development of phospholipids. The stimulus for developing this evolutionary sequence was the realization that cellular life was essential if Darwinian "survival of the fittest" was to direct evolution toward adaptation to the external environment.