[New mechanism in cell division].
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Cell Division↗
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[In vitro cell division kinetics in cells with normal and pathological karyotypes substituted by 5'bromodeoxyuridine (author's transl)].
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Adult↗
[Effect of the tick-borne encephalitis virus on the chromosomes and cell division in different cell cultures].
The mutagenic effect of tick-borne encephalitis virus (the Pan strain) was studied in chick embryo cells, Syrian hamster kidney cells and pig embryo kidney (SPEV) cell cultures showing different sensitivities to this virus. The dynamics of formation and types of chromosome damages were shown to be different in latent, subacute and acute forms of infection. Virus-induced chromosome aberrations appeared in the period of termination of the virus reproduction cycle. Differences in the effect of tick-borne encephalitis virus on the synthesis of nuclear DNA in chick embryo and SPEV cells were demonstrated. The experimental results suggest that a temporary increase of the mitotic activity observed in the inoculated cultures was due both to a delay of cells in one of the stages of the mitotic cycle (chick embryo and SPEV cells) and to a temporary stimulation of DNA synthesis (SPEV cells).
Animals↗
Revisiting the Drosophila microchaete lineage: a novel intrinsically asymmetric cell division generates a glial cell.
The bristle mechanosensory organs of the adult fly are composed of four different cells that originate from a single precursor cell, pI, via two rounds of asymmetric cell division. Here, we have examined the pattern of cell divisions in this lineage by time-lapse confocal microscopy using GFP imaging and by immunostaining analysis. pI divided within the plane of the epithelium and along the anteroposterior axis to give rise to an anterior cell, pIIb, and a posterior cell, pIIa. pIIb divided prior to pIIa to generate a small subepithelial cell and a larger daughter cell, named pIIIb. This unequal division, oriented perpendicularly to the epithelium plane, has not been described previously. pIIa divided after pIIb, within the plane of the epithelium and along the AP axis, to produce a posterior socket cell and an anterior shaft cell. Then pIIIb divided perpendicularly to the epithelium plane to generate a basal neurone and an apical sheath cell. The small subepithelial pIIb daughter cell was identified as a sense organ glial cell: it expressed glial cell missing, a selector gene for the glial fate and migrated away from the sensory cluster along extending axons. We propose that mechanosensory organ glial cells, the origin of which was until now unknown, are generated by the asymmetric division of pIIb cells. Both Numb and Prospero segregated specifically into the basal glial and neuronal cells during the pIIb and pIIIb divisions, respectively. This revised description of the sense organ lineage provides the basis for future studies on how polarity and fate are regulated in asymmetrically dividing cells.
Animals↗
Control of cell division by sex factor F in Escherichia coli. I. The 42.84-43.6 F segment couples cell division of the host bacteria with replication of plasmid DNA.
The F plasmid of Escherichia coli was used to study the genetic background of the control circuit in the bacteria that co-ordinates DNA replication and cell division of the host cells. When DNA replication of the F plasmid was blocked by growing cells carrying an amber-suppressible replication-defective F plasmid mutant under restrictive conditions, the cells continued to divide for about one generation until F plasmid was supposedly diluted to one copy per cell, and then they stopped dividing and formed non-septated filamentous cells. These observations suggest that completion of a round of replication is a necessary and sufficient condition of F DNA synthesis in the cell division of F+ bacteria; i.e. cell division of the F+ bacteria is coupled with DNA replication of the F plasmid. The observation that Giemsa-stainable materials in the filamentous cells were clustered in the center indicates that partitioning of chromosomal DNA (and presumably of F plasmid DNA) is also coupled with plasmid DNA replication. The function necessary for this coupling is carried by the 42.84-43.6 F (BamHI-PstI) segment, which is located outside the region essential for replication of the F plasmid. The nucleotide sequence demonstrates the existence of two open reading frames in this region, which encode polypeptides of 72 and 101 amino acids, respectively. These two reading frames are most likely to be transcribed as a single polycistronic message in the direction from the BamHI site at 42.84 F to the PstI site at 43.6 F. The expression of this "operon" is likely to be controlled by plasmid DNA replication.
Base Sequence↗
Diacylglycerol stimulates DNA synthesis and cell division in mouse 3T3 cells: role of Ca2+-sensitive phospholipid-dependent protein kinase.
The synthetic diacylglycerol 1-oleoyl-2-acetylglycerol competes directly with [3H]phorbol 12,13-dibutyrate for common binding sites in monolayer cultures of Swiss 3T3 cells and rapidly stimulates the phosphorylation of a Mr 80,000 cellular protein that has recently been shown to reflect the activation of protein kinase C in intact cells. Thus, this diacylglycerol provided a useful tool to determine whether exogenously added diacylglycerols can mimic the potent tumor promoter phorbol ester in eliciting DNA synthesis and cell division in quiescent cells. We found that OAG acts synergistically with insulin and other growth factors to stimulate reinitiation of cell proliferation, and several lines of evidence indicate that OAG shares with phorbol esters a common pathway of mitogenic action via stimulation of protein kinase C activity in intact 3T3 cells. The findings support the hypothesis that diacylglycerols represent endogenous analogs of phorbol esters and raise the possibility that diacylglycerols generated in the plasma membrane could act as a mitogenic signal for quiescent cells.
Animals↗
Studies on cell growth and cell division. I. A temperature-controlled system for inducing synchronous cell division.
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Cell Cycle↗
Synchronization of cell division in eight-cell bovine embryos produced in vitro: effects of nocodazole.
Current methods of arresting and synchronizing cell division have not been very successful and have had few applications in embryo studies. Our objective was to determine the reliability of a metaphase arrest agent, nocodazole, for halting and synchronizing blastomere division in cleavage-stage bovine embryos, and to verify its reversibility and toxicity in vitro. Eight-cell-stage embryos obtained at 58 hr postinsemination were treated with varying concentrations of nocodazole for 12 hr. Treated embryos were assessed for cleavage arrest, chromatin morphology, DNA synthesis, and histone H1 and myelin basic protein (MBP) kinase activity, and were scored for blastocyst formation and hatching rate. They were subsequently fixed to count the number of nuclei. Complete arrest of cell division was observed at concentrations of 0.4 micrograms ml-1 and above. Removal from nocodazole treatment led to immediate release from cleavage arrest, and was followed by synchronized mitosis, histone H1 kinase deactivation, and reentry into interphase within 3-5 hr. DNA synthesis was reinitiated at 6 hr after release. Although cell numbers and hatching rate decreased, the proportion of embryos reaching blastocyst stage was not significantly affected in nocodazole-treated embryos. It is concluded that nocodazole is a suitable choice for the cell-cycle synchronization of donor embryos for use in studies on the interactions between nucleus and cytoplasm during early embryogenesis.
Animals↗
Regulation of cell division in a human glioma cell clone by arachidonic acid and alpha-tocopherolquinone.
A human glioma cell clone (12-18 CV), derived from a previously characterized glioblastoma multiforme cell line, was established in culture. Lipid peroxidation (thiobarbituric acid test) occurred when either 8,11,14-eicosatrienoic acid or 5,8,11-eicosatetraenoic acid (arachidonic acid) was added to the cells in culture. The extent of lipid peroxidation was similar in fetal brain cells (CH II) treated with these polyunsaturated fatty acids. The antioxidant, alpha-tocopherolquinone, inhibited lipid peroxidation in both the glioma cell clone and fetal brain cells. Arachidonic acid significantly reduced cell division in both the glioma cell clone and fetal brain cells. alpha-Tocopherolquinone restored cell division to control levels in both cultures. These data show that cells from a tumor clone retain the capacity for lipid peroxidation. Furthermore, cell division in a tumor clone is correlated with lipid peroxidation in the same way that cell division in other cell lines is correlated with lipid peroxidation.
Arachidonic Acids↗
Mutations in the Caenorhabditis elegans gene vab-3 reveal distinct roles in fate specification and unequal cytokinesis in an asymmetric cell division.
Asymmetric cell divisions in which a precursor cell distributes fate potential unequally between the two daughter cells represent one of the major mechanisms for fate specification during development. Such mechanisms suggest at least two distinct cellular activities: factors that act to establish asymmetry in the precursor cell and factors that are distributed or activated unequally and function to make the daughter cells different from each other. In Caenorhabditis elegans, cytokinesis of the first division of the male-specific postembryonic blast cell B is unequal, and the two daughters adopt different fates. Others have observed that the genes lin-17 and lin-44 are required, respectively, to establish and to orient this asymmetric division. Mutations in lin-17 and lin-44 coordinately disrupt cytokinesis and fate specification. We describe the function of the gene vab-3 in the B cell lineage. Mutations in vab-3 disrupt the fate of the anterior daughter of B, B.a. However, unlike lin-17 and lin-44, mutations in vab-3 can disrupt fate without the corresponding disruption of unequal cytokinesis. Analysis of lin-17;vab-3 double mutants suggests that vab-3 acts after lin-17 for B.a. fate specification. Double mutant analysis has also identified additional functions of lin-17 in the B lineage subsequent to this first division.
Animals↗
Interaction between methyl CpG-binding protein and ran GTPase during cell division in tobacco cultured cells.
BACKGROUND AND AIMS: Methyl CpG-binding proteins are considered to play critical roles in epigenetic control of gene expression by recognizing and interacting with 5-methylcytosine (m(5)C) in eukaryotes. However, among 13 corresponding genes in Arabidopsis thaliana, designated as featuring a methyl-binding domain (MBD), only four have so far been shown actually to bind to m(5)C. One example, AtMBD5, was selected here to screen for interacting proteins. METHODS: Yeast two-hybrid assays were used for screening, and physical interaction was confirmed by pull-down and bimolecular fluorescence complementation (BiFC) assays. Cellular localization was analysed by fluorescence-tagged fusion proteins using tobacco (Nicotiana tabacum) cultured bright yellow 2 cells. KEY RESULTS: A gene finally identified was found to encode AtRAN3, a protein that belongs to the Ran GTPase family, which plays a critical role in nucleocytoplasmic transport and spindle bipolarization during cell division. AtMBD5 and AtRAN3 were clearly shown to interact in the nucleus by BiFC. On co-expression of AtMBD5-cyan fluorescence protein and yellow fluorescence protein-AtRAN3 in tobacco cells, both localized to the nucleus in the resting stage, migrating to the cytoplasm, primarily around chromatin, during mitosis, particularly at metaphase. CONCLUSIONS: These results suggest that AtMBD5 becomes localized to the vicinity of chromosomes with the aid of AtRAN3 during cell division, and may play an important role not only in maintenance of chromatin structures by binding to m(5)C, but also in progress through mitosis by detaching from m(5)C. The present findings also shed light on the physiological function of Ran GTPases, direct target proteins of which have not thus far been well defined, suggesting their key role in chromatin movements in plant cells.
Amino Acid Sequence↗
Cell division. II. A theoretical approach to chromosomal movements and the division of the cell.
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Cell Cycle↗
Cell division cycle of cultured neural precursor cells from Drosophila.
In Drosophila neuroblast cells, which give rise to the embryonic nervous system, undergo a limited number of asymmetric cell divisions. These cell lineages result in the formation of clusters of neurons when neuroblasts are isolated and cultured. A significant proportion of these neural cell clusters (NCC) arise from individual precursor cells. The formation of NCC containing more than two neurons is repressed when DNA synthesis is inhibited. Cell division during NCC development was examined by [3H]thymidine autoradiography. The pattern of DNA synthesis by neural cells was that expected based on observations in situ. The pattern in individual NCC was consistent with single precursor origins for more than 80% of NCC, under our conditions of culture. Based on this, we show that the largest neural precursors at gastrulation undergo the most cell divisions in culture. The neuroblast cell division cycle averages approximately 1.5 hr, and is similar to that of blastoderm cells.
Animals↗
Plane of cell cleavage and numb distribution during cell division relative to cell differentiation in the developing retina.
Progenitor cells in the early developing nervous system can divide symmetrically, giving rise to two daughter cells that divide again, or asymmetrically, giving rise to one cell that differentiates and one that divides again. It has been suggested that the orientation of the cell cleavage plane during mitosis determines the type of division. A marker of early cell differentiation, the RA4 antigen, was used to identify regions of the developing chick retina with and without differentiating cells, and the orientation of the cleavage plane was characterized for mitotic figures in each region. No difference was found in the frequency of any orientation between the regions with or without differentiating cells. Furthermore, in the region of the retina with differentiating cells, the RA4 antigen was present in mitotic figures with every possible orientation. Thus, the orientation of the cleavage plane appears to be unrelated to whether or not a division produces a cell that differentiates. It has also been suggested that the intracellular protein Numb mediates neurogenesis via asymmetric localization during cell division. Numb localization was compared with expression of markers of early cell differentiation, the RA4 antigen and Delta. Differentiating and nondifferentiating cells were found both with and without Numb expression. Cells with a cleavage plane parallel to the retinal surface were polarized, such that Numb and/or the RA4 antigen, when present, were only in the daughter cell farthest from the ventricle. These findings indicate a need to reconsider current hypotheses regarding the key features underlying symmetric and asymmetric divisions in the developing nervous system.
Animals↗
Cell division in a species of Erwinia IV. Metabolic blocks in panothenate biosynthesis and their relationship to inhibition of cell division.
Grula, Mary M. (Oklahoma State University, Stillwater) and E. A. Grula. Cell division in a species of Erwinia. IV. Metabolic blocks in pantothenate biosynthesis and their relationship to inhibition of cell division. J. Bacteriol. 83:989-997. 1962.-Four compounds that inhibit cell division in an Erwinia sp., d-serine, d-histidine, d-phenylalanine, and penicillin, decrease the intracellular pantothenate content of Erwinia at culture ages of 10 and 16 hr. In the case of penicillin, it appears to be the result of excessive leakage from long cells; however, with the three d-amino acids, there is a genuine inhibition of synthesis. Among agents tested that reverse the inhibition of division, only pantoyl lactone, and to a lesser extent, omega-methylpantoyl lactone, restore intracellular content of pantothenate. This restoration is considerably less effective with d-serine as a division-inhibiting agent than with the others. Other lactones, l-alpha-alanine, and ammonium chloride are ineffective, or only slightly effective, in restoring pantothenate synthesis. Effects of division-inhibiting compounds and reversing agents upon cellular coenzyme A activity in general parallel their effects on pantothenate synthesis. There is no direct correlation between ability of a compound to reverse cell-division inhibition and ability to restore synthesis of either pantothenic acid or coenzyme A. Evidence is presented that d-serine interferes with the utilization of aspartic acid and also blocks synthesis of pantoic acid. Compounds (including glucose) which tend to produce long cells result in the accumulation of pyruvic acid in the growth medium. Pantoic acid reduces, and pantoyl lactone abolishes completely, this accumulation of pyruvate. Other reversing agents do not abolish the pyruvate accumulation.
Amino Acids↗
Possible role of tyrosine kinases in the prolactin stimulation of cell division in Nb2 node lymphoma cells.
Orthovanadate and genistein were employed to determine the possible role of tyrosine kinase in the prolactin stimulation of cell division in Nb2 node lymphoma cells. Orthovanadate (0.1-0.25 microM), an inhibitor of specific phosphatases, was found to stimulate cell division as well as potentiate the mitogenic effect of prolactin on Nb2 cells when prolactin was employed at a less than maximum stimulatory concentration. Genistein, an inhibitor of tyrosine kinase, was found to inhibit the prolactin stimulation of cell division. Since prolactin was shown in earlier studies to stimulate the phosphorylation of tyrosyl residues in specific Nb2 cell proteins, these results suggest that the signal transduction pathway for the prolactin stimulation of cell division in the Nb2 node lymphoma cells likely involves the participation of tyrosine kinase(s).
Animals↗
Anti-IgM but not anti-IgD antibodies inhibit cell division of normal human mature B cells.
Insolubilized anti-IgD antibody markedly increased DNA synthesis in and cell division of normal peripheral blood B cells (PBL-B) when used in combination with IL-4. Anti-IgM antibodies also induced DNA synthesis of PBL-B, but their ability to induce cell division was less than that of anti-IgD antibodies even when used in combination with IL-4. Moreover, anti-IgM antibodies inhibited cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4 without affecting DNA synthesis. Anti-IgM antibodies also inhibited Staphylococcus aureus Cowan I-induced cell division of PBL-B without affecting DNA synthesis. These results indicate that cross-linkage of surface IgM (sIgM) in mature B cells generates negative signals to inhibit cell division of mature B cells. Because anti-IgD antibodies did not inhibit cell division at all, the role of sIgD in the regulation of cell division of mature B cells may be quite different from that of sIgM. IFN-alpha/beta promoted cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4. They also counteracted the inhibitory effect of anti-IgM antibody on cell division of PBL-B.
Antibodies, Anti-Idiotypic↗
Bacterial SOS checkpoint protein SulA inhibits polymerization of purified FtsZ cell division protein.
Cell division of Escherichia coli is inhibited when the SulA protein is induced in response to DNA damage as part of the SOS checkpoint control system. The SulA protein interacts with the tubulin-like FtsZ division protein. We investigated the effects of purified SulA upon FtsZ. SulA protein inhibits the polymerization and the GTPase activity of FtsZ, while point mutant SulA proteins show little effect on either of these FtsZ activities. SulA did not inhibit the polymerization of purified FtsZ2 mutant protein, which was originally isolated as insensitive to SulA. These studies define polymerization assays for FtsZ which respond to an authentic cellular regulator. The observations presented here support the notion that polymerization of FtsZ is central to its cellular role and that direct, reversible inhibition of FtsZ polymerization by SulA may account for division inhibition.
Bacterial Proteins↗