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PubMed1982

Effect of exogenous gangliosides on human neural cell division.

Human neural cells in exponential growth phase were transferred to a serum-free medium and maintained for 72 hr without any detectable loss in viability. The two normal fetal cell lines (CHI and CHII) showed a serum-dependent cell proliferation, but the glioblastoma multiforme cells (12-18) were able to continue proliferating in this totally synthetic medium. The incorporation of [3H]thymidine into the acid-precipitable fraction of both normal and neoplastic human neural cells was assayed in the presence and the absence of exogenous gangliosides by a convenient new method. In serum-free medium, gangliosides (50 microM) inhibited the thymidine incorporation into the normal fetal cells within 24 hr and, in serum containing medium, reduced their proliferation within 48 hr. No such effects were detectable in the glioma cells. The inhibition of thymidine incorporation in the normal cells was reversible upon removal of the gangliosides. These results indicate a role of gangliosides in the postmitotic phase of normal human neural cells resulting in the regulation of cell proliferation.

Brain↗
PubMed1985

[Effect of UV irradiation on the mitotic cycle of Chinese hamster cells with varying UV sensitivity. II. The temporal relations in blocked cell division].

Analysis of cell distribution through phases of the cell cycle by the method of DNA flow cytofluorimetry has been utilized to investigate effects of UV light on the first cycle after irradiation in asynchronous Chinese hamster cells with different UV-sensitivity: V79 cell line (UV resistant cells) and UV-sensitive clones CHS2 and XII. Immediately after irradiation colcemid was added to the cultures to prevent mitosis and re-entering the cell cycle. UV irradiation did not affect the rate of cell passing from G1 into S phase in UV resistant cells. In UV irradiated cultures of UV-sensitive cells, a large portion of cells was arrested in G1, the effect increasing with UV dose. Besides, a portion of cells in S phase increased and the number of cells entering the G2+M compartment was essentially reduced in UV irradiated cultures of UV-sensitive cells much more than in V79 cells. The results may point to an inhibition of replicon initiation, and a larger DNA chain elongation in UV-sensitive clones after UV irradiation.

Animals↗
PubMed2001

Water deficit inhibits cell division and expression of transcripts involved in cell proliferation and endoreduplication in maize endosperm.

Water deficit at the early post-pollination stage in cereal grains decreases endosperm cell division and, in turn, decreases the capacity for storage material accumulation. Post-mitotic replication of nuclear DNA (endoreduplication) may also play a role in stress effects. To gain a better understanding of the extent to which cell proliferation and endoreduplication are affected by water deficit, nuclear numbers and size were examined in endosperms of maize (Zea mays L.) by flow cytometry and the transcript levels of genes which have recognized roles in the cell cycle were quantified. Water deficit from 5-13 d after pollination (DAP) decreased the rate of endosperm cell division by 90% and inhibited [3H]-thymidine incorporation into DNA from 9-13 DAP. The proportion of nuclei engaging in endoreduplication and nuclear DNA content increased steadily from 9-13 DAP in controls, but water deficit initially increased the proportion of endoreduplicating nuclei at 9 DAP, then halted further entry into endoreduplication and S-phase cycling from 9-13 DAP. Transcript levels of alpha-tubulin, and the S-phase gene products histone H3 and PCNA were not affected by water deficit until 13 DAP, whereas those of ZmCdc2, a cyclin dependent kinase (CDK) with regulatory roles in mitosis, were inhibited substantially from 9-13 DAP. Cell proliferation and associated processes were inhibited at initial stages of the stress episode, whereas endoreduplication and associated S-phase processes were not inhibited until the stress was more advanced. It was concluded that endosperm mitosis has greater sensitivity than endoreduplication to water deficit.

Adaptation, Physiological↗
PubMed2003

Cytokinesis: relative alignment of the cell division apparatus and the mitotic spindle.

The cell division apparatus is assembled at different stages of the cell cycle in different eukaryotic organisms. Mechanisms exist in all organisms, however, to ensure that the cell division apparatus and the mitotic spindle are aligned perpendicular to each other. Such an alignment ensures that each daughter cell receives a nucleus and that the cell division apparatus does not cleave and destroy the genetic material. The interaction(s) of astral microtubules with the cell cortex appears to play an important role in establishing perpendicularity between chromosome segregation and cell division machinery.

Animals↗
PubMed2001

Crystal structure of the bacterial cell division inhibitor MinC.

Bacterial cell division requires accurate selection of the middle of the cell, where the bacterial tubulin homologue FtsZ polymerizes into a ring structure. In Escherichia coli, site selection is dependent on MinC, MinD and MINE: MinC acts, with MinD, to inhibit division at sites other than the midcell by directly interacting with FTSZ: Here we report the crystal structure to 2.2 A of MinC from Thermotoga maritima. MinC consists of two domains separated by a short linker. The C-terminal domain is a right-handed beta-helix and is involved in dimer formation. The crystals contain two different MinC dimers, demonstrating flexibility in the linker region. The two-domain architecture and dimerization of MinC can be rationalized with a model of cell division inhibition. MinC does not act like SulA, which affects the GTPase activity of FtsZ, and the model can explain how MinC would select for the FtsZ polymer rather than the monomer.

Amino Acid Sequence↗
PubMed1981

An inducible DNA replication-cell division coupling mechanism in E. coli.

Cell division is a tightly regulated periodic process. In steady-state cultures of Enterobacteriaceae, division takes place at a well defined cell mass and is strictly coordinated with DNA replication. In wild-type Escherichia coli the formation of cells lacking DNA is very rare, and interruptions of DNA replication arrest cell division. The molecular bases of this replication-division coupling have been elusive but several models have been proposed. It has been suggested, for example, that the termination of a round of DNA replication may trigger a key event required for cell division. A quite different model postulates the existence of a division inhibitor which prevents untimely division and whose synthesis is induced to high levels when DNA replication is perturbed. The work reported here establishes the existence of the latter type of replication-division coupling in E. coli, and shows that the sfiA gene product is an inducible component of this division inhibition mechanism which is synthesized at high levels after perturbations of DNA replication.

Bacterial Proteins↗
PubMed2002

Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo.

Controlling cell division is fundamental. One environmental cue that exerts profound control over both the orientation and frequency of cell division in vivo is a naturally occurring, wound-induced electric field (EF). Wounds in rat corneas generate endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD; +40 mV internally positive) collapses at the wound edge, but is maintained at normal levels at 0.5 mm back from the wound. We manipulated the endogenous EF this creates by using drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacologically, respectively increased or decreased the extent of oriented cell division. In addition, cells closest to the wound edge, where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Because the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.

Aminophylline↗
PubMed1996

Abnormal cell divisions in leaf primordia caused by the expression of the rice homeobox gene OSH1 lead to altered morphology of leaves in transgenic tobacco.

Transgenic tobacco plants were generated carrying a rice homeobox gene, OSH1, controlled by the promoter of a gene encoding a tobacco pathogenesis-related protein (PR1a). These lines were morphologically abnormal, with wrinkled and/or lobed leaves. Histological analysis of shoot apex primordia indicates arrest of lateral leaf blade expansion, often resulting in asymmetric and anisotrophic growth of leaf blades. Other notable abnormalities included abnormal or arrested development of leaf lateral veins. Interestingly, OHS1 expression was undetectable in mature leaves with the aberrant morphological features. Thus, OSH1 expression in mature leaves is not necessary for abnormal leaf development. Northern blot and in situ hybridization analyses indicate that PR1a-OSH1 is expressed only in the shoot apical meristem and in very young leaf primordia. Therefore, the aberrant morphological features are an indirect consequence of ectopic OSH1 gene expression. The only abnormality observed in tissues expressing the transgene was periclinal (rather than anticlinal) division in mesophyll cells during leaf blade initiation. This generates thicker leaf blades and disrupts the mesophyll cell layers, from which vascular tissues differentiate. The OSH1 product appears to affect the mechanism controlling the orientation of the plane of cell division, resulting in abnormal periclinal division of mesophyll cell, which in turn results in the gross morphological abnormalities observed in the transgenic lines.

Cell Division↗
PubMed1987

Cell division in migratory and aggregated neural crest cells in the developing gut: an experimental approach to innervation-related motility disorders of the gut.

Extensive studies in the chicken embryo have recently supplied more insights into the development of the enteric nervous system, which mainly derives from the vagal neural crest (i.e., the neural crest opposite somites 1 to 7). Crest cells migrate from this region to and via the developing gut. By means of a double labeling technique of both neural crest cells and cells in the S-phase of the cell cycle, we found that these migrating crest cells still proliferate in the gut. Some cells even go through cell division after the formation of a nerve plexus. Some implications for the pathogenesis of congenital innervation abnormalities such as hyperganglionosis and the aganglionosis of Hirschsprung's disease are discussed.

Animals↗
PubMed2005

Arabidopsis TCP20 links regulation of growth and cell division control pathways.

During postembryonic plant development, cell division is coupled to cell growth. There is a stringent requirement to couple these processes in shoot and root meristems. As cells pass through meristems, they transit through zones with high rates of cell growth and proliferation during organogenesis. This transition implies a need for coordinate regulation of genes underpinning these two fundamental cell functions. Here, we report a mechanism for coregulation of cell division control genes and cell growth effectors. We identified a GCCCR motif necessary and sufficient for high-level cyclin CYCB1;1 expression at G2/M. This motif is overrepresented in many ribosomal protein gene promoters and is required for high-level expression of the S27 and L24 ribosomal subunit genes we examined. p33(TCP20), encoded by the Arabidopsis TCP20 gene, binds to the GCCCR element in the promoters of cyclin CYCB1;1 and ribosomal protein genes in vitro and in vivo. We propose a model in which organ growth rates, and possibly shape in aerial organs, are regulated by the balance of positively and negatively acting teosinte-branched, cycloidea, PCNA factor (TCP) genes in the distal meristem boundary zone where cells become mitotically quiescent before expansion and differentiation.

Arabidopsis↗
PubMedDate not supplied

Movement of a cytokinesis factor cdc12p to the site of cell division.

A key question in cytokinesis is how the plane of cell division is positioned within the cell. Although a number of cytokinesis factors involved in formation of the actomyosin contractile ring have been identified, little is known about how these factors are localized and assembled at the cell-division site. Cells of the fission yeast Schizosaccharomyces pombe divide using a medial actomyosin ring that assembles in early mitosis [1]. The S. pombe cdc12 gene encodes a formin, a member of a family of proteins that have functions in cytokinesis and cell polarity and that may bind Rho/Cdc42 GTPases, profilin and other actin-associated proteins [1] [2] [3] [4]. The cdc12 protein (cdc12p) is required specifically for medial-ring assembly during cytokinesis and is a component of this ring [2] [5]. In this study, cdc12p was found, during interphase, in a discrete, motile cytoplasmic spot that moved to the future site of cell division at the onset of mitosis. Three lines of evidence indicated that this cdc12p spot moved on both actin and microtubule networks: movement required either actin or microtubules; the spot was associated with actin and microtubule structures; and individual spots were seen to move along both microtubule and non-microtubule tracks. These findings demonstrate that a cytokinesis factor may travel on both microtubule and actin networks to the future site of cell division.

Actins↗
PubMed1994

Patterns of cell division revealed by transcriptional regulation of genes during the cell cycle in plants.

Transcripts from five cell cycle related genes accumulate in isolated cells dispersed throughout the actively dividing regions of plant meristems. We propose that this pattern reflects gene expression during particular phases of the cell division cycle. The high proportion of isolated cells suggests that synchrony between daughter cells is rapidly lost following mitosis. This is the first time that such a cell specific expression pattern has been described in a higher organism. Counterstaining with a DNA specific dye revealed that transcripts from three genes (two mitotic cyclins and a cdc2-like gene) accumulate during part of interphase and early mitosis whereas transcripts from a histone H4 gene are preferentially detected only in interphase cells. Double labelling for cyclin and histone H4 transcripts confirms that these genes are expressed in different cells, and therefore at different phases of the cell cycle. The results suggest that transcriptional regulation of cell cycle related genes may be important in controlling cell division in plants, and that these genes are useful markers for identifying cells at specific phases of the cell cycle within plant meristems.

Amino Acid Sequence↗
PubMed1995

Dominant negative mutants of the Cdc2 kinase uncouple cell division from iterative plant development.

Because plant cells do not move and are surrounded by a rigid cell wall, cell division rates and patterns are believed to be directly responsible for generating new structures throughout development. To study the relationship between cell division and morphogenesis, transgenic tobacco and Arabidopsis plants were constructed expressing dominant mutations in a key regulator of the Arabidopsis cell cycle, the Cdc2a kinase. Plants constitutively overproducing the wild-type Cdc2a or the mutant form predicted to accelerate the cell cycle did not exhibit a significantly altered development. In contrast, a mutation expected to arrest the cell cycle abolished cell division when expressed in Arabidopsis, whereas some tobacco plants constitutively producing this mutant protein were recovered. These plants had a reduced histone H1 kinase activity and contained considerably fewer cells. These cells were, however, much larger and underwent normal differentiation. Morphogenesis, histogenesis and developmental timing were unaffected. The results indicate that, in plants, the developmental controls defining shape can act independently from cell division rates.

Amino Acid Sequence↗
PubMed2003

Toward an understanding of cell growth and the cell division cycle of unicellular photoautotrophic cyanobacteria.

The cell division cycle of Synechococcus sp. strain PCC 6301 in light is characterized by the sequential and orderly appearance of macromolecular synthesis periods. In the dark, macromolecular synthesis and cell division are severely curtailed. When dark-incubated cultures are reexposed to light, a new cell cycle is initiated. The pattern of the cell events displayed by Synechococcus in light and the absence of sustained growth in dark incubation conditions suggests that light-activated regulatory molecules control macromolecular synthesis and the cell division cycle. For example, ribosomal RNA synthesis is stimulated by a light-activated DNA binding factor in light but not in the dark. Light/dark conditions induce cell synchrony in Prochlorococcus. Distinct G1, S and G2 phases characterize cell cycles of marine Synechococcus and Prochlorococcus. Cell division in Synechococcus elongatus PCC 7942 and marine Synechococcus is controlled by circadian oscillators.

Cell Cycle↗
PubMed1998

Differentiation of naive CTL to effector and memory CTL: correlation of effector function with phenotype and cell division.

Phenotypically and functionally, the early steps of T cell differentiation are not well characterized. In addition, the effector T cell stage shares several phenotypic characteristics with memory T cells, which has made the analysis of T cell memory difficult. In this study, we have investigated in vitro and in vivo the differentiation of naive CTL into effector and memory CTL as a function of cell division using lymphocytic choriomeningitis virus-specific TCR-transgenic spleen cells labeled with the vital dye carboxyfluorescein diacetate, succinimidyl ester. The following major points emerged. 1) During the first nine cell divisions, the investigated cell surface markers were strongly modulated. 2) The TCR was stepwise down-regulated during viral infection. 3) Cytotoxic effector function was acquired within one cell division and was retained during the next four to five divisions. 4) In vitro, CTL reached a CD44highCD62L+ memory phenotype after 6-10 cell divisions and required restimulation to exert effector function. 5) Lymphocytic choriomeningitis virus memory mice contained two distinct memory populations: a CD44highCD62L- population, predominately located in the spleen and exerting rapid effector function, and a CD44highCD62L+ population found in the spleen and the lymph nodes, which had lost immediate effector function. This finding suggests that two types of memory CTL exist. The correlation between CD62L expression, effector function, and Ag persistence is discussed.

Adoptive Transfer↗
PubMed1986

Dependency of B cells on the presence of adherent cells, or factors derived from them, for the production of autoantibodies in vitro in the absence of cell division.

Peritoneal cells from untreated mice secrete autoantibodies after 3-4 days of in vitro culture, although the cells do not divide. Here, peritoneal cells enriched for B cells to contain 95% surface Ig-bearing cells, did not secrete autoantibodies after 3 days of in vitro culture unless plastic-adherent cells derived from the peritoneal cavity were cultured with the B cells. Cell-free media, taken from peritoneal adherent cells that had been cultured for 3 days in vitro, when added a final concentration of 50% in fresh culture medium to purified B cells, substituted for the presence of accessory cells. In contrast to cultures of unfractionated peritoneal cells, little increase in precursor frequency was detected when enriched B cells were cultured in the presence of LPS/DXS. However, the addition of adherent cells, supernatants derived from adherent cells, or cytokines produced by a T-cell hybrid EL4, resulted in an increased precursor frequency when LPS/DXS was added to the culture medium. Three macrophage cell lines, P388-D1, J774, and PU-5-IR, when added to purified B cells. augmented the autoantibody precursor frequency detected in vitro. This is strong evidence that potentially autoreactive B cells require one or more types of accessory cells in order to differentiate into autoantibody secretors during culture in vitro. Further, the results provide indirect evidence that interleukin 1 may be a crucial molecule in the differentiation of B cells.

Animals↗
PubMed1996

Effects of insulin-like growth factors and binding protein 1 on bovine granulosa cell division in anchorage-independent culture.

Granulosa cells can exhibit the properties of stem cells and tumour cells. Contact with neighbouring cells does not inhibit their replication in vivo and they can divide in vitro while embedded in agar and thus without anchorage on a substratum. By culturing granulosa cells without anchorage, those cells that do not require anchorage, and thus exhibit at least one property of stem cells, divide. The effects of insulin-like growth factors (IGFs) and insulin-like growth factor binding protein 1 (IGFBP-1) on the replication of such cells was investigated by isolating granulosa cells from follicles (3-5 mm diameter) from cyclic cows and culturing them in soft agar-methylcellulose solution. Cell division was measured as [3H]thymidine incorporation into DNA, total DNA, or as the amount of the nuclear La antigen. This antigen is involved in RNA synthesis and is expressed ubiquitously; here it was used to estimate the number of cells indirectly. Both IGF-I (100 ng ml-1) and IGF-II (100 ng ml-1) and their respective analogues, as well as insulin, all at the same concentration, significantly increased DNA synthesis as determined by [3H]thymidine incorporation (n = 5). An increase in the number of cells in the presence of IGF-I was also confirmed by DNA measurement (P < 0.05, n = 5) and by western immunoblotting analyses of La antigen (n = 3). IGFBP-1 significantly inhibited cell division stimulated by IGF-I (P < 0.001) and IGF-II (P < 0.001), but not that stimulated by the analogue, LR3IGF-I, which has low affinity for IGFBPs. Other factors also known to affect IGF synthesis or effectiveness (FSH, oestradiol, growth hormone) did not appear to influence division of granulosa cells when cultured under anchorage-independent conditions, while dibutyryl cAMP significantly inhibited cell division (P < 0.01, n = 5). In conclusion, IGFs have a role to play in stimulating division of stem-cell-like granulosa cells during follicular development and IGFBP-1 can specifically inhibit the mitogenic effects of IGFs.

Animals↗