Endoreduplication

Endoreduplication (also referred to as endoreplication or endocycling) is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity. Examples of endoreplication characterized in arthropod, mammalian, and plant species suggest that it is a universal developmental mechanism responsible for the differentiation and morphogenesis of cell types that fulfill an array of biological functions. While endoreplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that polyploidy can be detected in the majority of plant tissues. Endoreduplication (also referred to as endoreplication or endocycling) is replication of the nuclear genome in the absence of mitosis, which leads to elevated nuclear gene content and polyploidy. Endoreplication can be understood simply as a variant form of the mitotic cell cycle (G1-S-G2-M) in which mitosis is circumvented entirely, due to modulation of cyclin-dependent kinase (CDK) activity. Examples of endoreplication characterized in arthropod, mammalian, and plant species suggest that it is a universal developmental mechanism responsible for the differentiation and morphogenesis of cell types that fulfill an array of biological functions. While endoreplication is often limited to specific cell types in animals, it is considerably more widespread in plants, such that polyploidy can be detected in the majority of plant tissues. Endoreplicating cell types that have been studied extensively in model organisms Endoreplication, endomitosis and polytenization are three somewhat different processes resulting in polyploidization of a cell in a regulated manner. In endoreplication cells skip M phase completely, resulting in a mononucleated polyploid cell. Endomitosis is a type of cell cycle variation where mitosis is initiated, but some of the processes are not completed. Depending on how far the cell progresses through mitosis, this will give rise to a mononucleated or binucleated polyploid cell. Polytenization arises with under- or overamplification of some genomic regions, creating polytene chromosomes. Based on the wide array of cell types in which endoreplication occurs, a variety of hypotheses have been generated to explain the functional importance of this phenomenon. Unfortunately, experimental evidence to support these conclusions is somewhat limited: Cell ploidy often correlates with cell size, and in some instances, disruption of endoreplication results in diminished cell and tissue size suggesting that endoreplication may serve as a mechanism for tissue growth. Relative to mitosis, endoreplication does not require cytoskeletal rearrangement or the production of new cell membrane and it often occurs in cells that have already differentiated. As such it may represent an energetically efficient alternative to cell proliferation among differentiated cell types that can no longer afford to undergo mitosis. While evidence establishing a connection between ploidy and tissue size is prevalent in the literature, contrary examples also exist. In developing plant tissues the transition from mitosis to endoreplication often coincides with cell differentiation and morphogenesis. However it remains to be determined whether endoreplication and polypoidy contribute to cell differentiation or vice versa. Targeted inhibition of endoreplication in trichome progenitors results in the production of multicellular trichomes that exhibit relatively normal morphology, but ultimately dedifferentiate and undergo absorption into the leaf epidermis. This result suggests that endoreplication and polyploidy may be required for the maintenance of cell identity. Endoreplication is commonly observed in cells responsible for the nourishment and protection of oocytes and embryos. It has been suggested that increased gene copy number might allow for the mass production of proteins required to meet the metabolic demands of embryogenesis and early development. Consistent with this notion, mutation of the Myc oncogene in Drosophila follicle cells results in reduced endoreplication and abortive oogenesis. However, reduction of endoreplication in maize endosperm has limited effect on the accumulation of starch and storage proteins, suggesting that the nutritional requirements of the developing embryo may involve the nucleotides that comprise the polyploid genome rather than the proteins it encodes. Another hypothesis is that endoreplication buffers against DNA damage and mutation because it provides extra copies of important genes. However, this notion is purely speculative and there is limited evidence to the contrary. For example, analysis of polyploid yeast strains suggests that they are more sensitive to radiation than diploid strains. Research in plants suggests that endoreplication may also play a role in modulating stress responses. By manipulating expression of E2fe (a repressor of endocycling in plants), researchers were able to demonstrate that increased cell ploidy lessens the negative impact of drought stress on leaf size. Given that the sessile lifestyle of plants necessitates a capacity to adapt to environmental conditions, it is appealing to speculate that widespread polyploidization contributes to their developmental plasticity