Drive Cell Division Research Articles

Quantitative analysis of cell division in leaves: methods, developmental patterns and effects of environmental conditions.

In planta quantitative studies of cell cycle are necessary for examining the role of cell division in the response of plants to environmental conditions and to analyse the behaviour of transformed plants in this context. We present and discuss non-intrusive kinematic methods which allow estimating the duration of cell cycle with a high spatial resolution in the leaf. Different methods are proposed and discussed for monocotyledons and dicotyledons, and compared with methods involving the use of chemicals. In monocotyledon leaves, cell division is restricted to a limited zone near the leaf insertion point, twice as long in the mesophyll as in the epidermis. In dicotyledons, cell division occurs in the whole leaf with a uniform and constant cell cycle duration for a determinate number of cell cycles, representing about half of leaf development. Over several experiments, this number is well conserved in a given leaf zone in the absence of stresses, but larger near the leaf base than near the leaf tip. After that, cell cycle duration increases because cells are progressively blocked in G1 while the durations of S-G2-M phases do not change with time. Leaf temperature affects neither the distribution of nuclei in each phase of the cycle nor the number of cell cycles in a leaf. Water or light deficits both cause a partial blockage of nuclei in G1 during the stress only, thereby increasing cell cycle duration and decreasing final cell number. These results suggest that a strong developmental programme drives cell division in leaves, so a simple framework allows analysis of temporal patterns, of spatial gradients and of the effect of environmental conditions.

Genomic components of carcinogenesis

Many of the genes encoding growth factors, growth factor receptors, enzymes, and other effector molecules that regulate normal cell growth are designated protooncogenes. Oncogenes, those genes associated with cellular transformation, differ from their protooncogenic progenitors by being mutated, overexpressed, or expressed at inappropriate times or locations in the cell. One of the activities of growth factors is to prime cells to undergo programmed cell death, which is characterized by a series of morphologic changes called apoptosis. In normal cells, specific mediators must be activated or suppressed to bypass programmed cell death. In tumor cells, either the pathways leading to apoptosis are not functional or the mediators that normally "rescue" cells from this fate are overexpressed or constitutively activated. In addition to the biochemical pathways that drive cell division, there are others that limit cell proliferation; these, designated tumor suppressors, anti-oncogenes, or recessive oncogenes, must be inactivated in normal cells to allow passage through the cell cycle and cell proliferation. In contrast to oncogenes, which are overexpressed or activated in tumors, tumor-suppressor genes are frequently inactivated in tumor cells, either by mutation or deletion. Thus, in normal cells a series of checks and balances must be overcome to allow initiation and continuation of cell division. In tumors, these processes are aberrant, resulting in increased rates of cell division, increases in the proportion of cells in the cell cycle, or increased survival of activated cells. Therefore, tumor cells frequently accumulate genomic alterations, which may result in the activation of a particular array of oncogenes, the inactivation of specific tumor-suppressor genes, and the bypassing of programmed cell death. Trials of antitumor agents that act by exploiting the overexpression of oncogenes in tumors and of the biochemical pathways by which they mediate cell proliferation are currently underway.

Oncogenes and tumor suppressor genes.

The artificial selection of the directly acting or acute RNA tumor viruses for high transforming ability has led to the isolation of defective retroviral genomes that have picked up, by accidental recombination, some of the important genes that influence, trigger or regulate cell division. These genes belong to at least four functionally different groups. Each of them can contribute to tumor development and/or progression after activation by structural or regulatory changes. Growth factor genes may act as oncogenes following constitutive activation in a cell that normally responds to, but does not produce, the corresponding growth factor (the autocrine model, exemplified by sis). Growth factor receptors may be fixed in a state of continuous, faulty signalling by the truncation of their external, ligand binding portion (examples: erb-B, fms). Genes coding for proteins involved in signal transduction may be activated by point mutations in certain, important domains (example: the ras-family). DNA binding proteins, presumably involved in DNA replication may drive cell division after constitutive activation by retroviral insertion, chromosomal translocation or gene amplification (example: the myc-family).