Regulation Of Endoreduplication Research Articles

Folate-depletion alters mouse trophoblast stem cell regulation in vitro

Maternal folate deficiency increases risk of congenital malformations, yet its effect on placenta development is unclear. Here, we investigated how folate-depleted culture medium affects the developmental potential of mouse trophoblast stem cells (TSCs). When cultured in stem cell conditions, TSC viability was unaffected by folate depletion, but ectopic differentiation of trophoblast cell subtypes occurred. When cultured in conditions that promote differentiation, folate-depleted TSCs were driven towards a syncytiotrophoblast cell fate potentially at the expense of other lineages. Additionally, trophoblast giant cell nuclei were small implicating folate in the regulation of endoreduplication. Therefore, dietary folate intake likely promotes trophoblast development.

Role of cell cycling and polyploidy in placental trophoblast of different mammalian species.

The trophoblast cells that take part in placenta formation are characterized by different modes of multiplication of their genome that largely designates their eu- or aneuploidy level. The two main ways of genome multiplication are described in different degree: (a) endoreduplication that involves almost complete shutdown of mitosis and (b) reduced mitosis ('endomitosis') in which, by contrast, entry into mitosis and the passage of its initial stages is a prerequisite of genome multiplication. Endoreduplication observed in the trophoblast giant cells (TGC) in a range of mammalian species implies uncoupling of DNA replication from mitosis achieved by reduction of mitotic Cdk activity. The key role in the regulation of endoreduplication and endomitosis play activity of APC/C complex, geminin and E2F family. A programme of genome multiplication and cell cycle progression may include depolyploidization achieved by specific mitotic or non-mitotic (amitotic) division of the giant nucleus. In some mammalian species (Rodents), this process represents the final step of the giant cell lifespan that coincides with complete cessation of cell or genome reproduction. Meantime, in other species the process may take part in cell reproduction during lengthy pregnancy. The dynamics of fox and human polyploidization is similar by the possibility of a simultaneous increase in the proportion of endopolyploid and low-polyploid cells. Reduced mitoses, endoreduplication and depolyploidization appear to be an evolution strategy allowing to generate the functionally different trophoblast cell populations depending of the lifestyle of life of the animal species. Some placental pathologies may be accounted for disturbance of the programme of the cell/genome reproduction of the giant and low-ploid cell populations.

MIDGETconnectsCOP1‐dependent development with endoreduplication inArabidopsis thaliana

In Arabidopsis thaliana, loss of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) function leads to constitutive photomorphogenesis in the dark associated with inhibition of endoreduplication in the hypocotyl, and a post-germination growth arrest. MIDGET (MID), a component of the TOPOISOMERASE VI (TOPOVI) complex, is essential for endoreduplication and genome integrity in A.thaliana. Here we show that MID and COP1 interact in vitro and in vivo through the amino terminus of COP1. We further demonstrate that MID supports sub-nuclear accumulation of COP1. The MID protein is not degraded in a COP1-dependent fashion in darkness, and the phenotypes of single and double mutants prove that MID is not a target of COP1 but rather a necessary factor for proper COP1 activity with respect to both, control of COP1-dependent morphogenesis and regulation of endoreduplication. Our data provide evidence for a functional connection between COP1 and the TOPOVI in plants linking COP1-dependent development with the regulation of endoreduplication.

Arabidopsis CAPRICE-LIKE MYB 3(CPL3) controls endoreduplication and flowering development in addition to trichome and root hair formation

CAPRICE (CPC) encodes a small protein with an R3 MYB motif and promotes root hair cell differentiation in Arabidopsis thaliana. Three additional CPC-like MYB genes, TRY (TRIPTYCHON), ETC1 (ENHANCER OF TRY AND CPC 1) and ETC2 (ENHANCER OF TRY AND CPC 2) act in a redundant manner with CPC in trichome and root hair patterning. In this study, we identified an additional homolog, CPC-LIKE MYB 3 (CPL3), which has high sequence similarity to CPC, TRY, ETC1 and ETC2. Overexpression of CPL3 results in the suppression of trichomes and overproduction of root hairs, as has been observed for CPC, TRY, ETC1 and ETC2. Morphological studies with double, triple and quadruple homolog mutants indicate that the CPL3 gene cooperatively regulates epidermal cell differentiation with other CPC homologs. Promoter-GUS analyses indicate that CPL3 is specifically expressed in leaf epidermal cells, including stomate guard cells. Notably, the CPL3 gene has pleiotropic effects on flowering development, epidermal cell size and trichome branching through the regulation of endoreduplication.

Identification of quantitative trait loci that affect endoreduplication in maize endosperm

Endoreduplication in maize endosperm precedes the onset of starch and storage protein synthesis, and it is generally thought to influence grain filling. We created four backcross populations by reciprocally crossing the F(1) progeny of a cross between Sg18 and Mo17 to the parental inbreds, which differ in endoreduplication by two parameters--mean ploidy and percentage of endoreduplicated nuclei. This four-backcross design allowed us to estimate and test the additive and dominant genetic effects of quantitative trait loci (QTLs) affecting endoreduplication. An analysis of endosperm from the four backcross populations at 16 days after pollination using a modified triploid mapping approach identified three endosperm QTLs influencing mean ploidy and two endosperm QTLs affecting the percentage of endoreduplicated nuclei. Some of these QTLs may manifest their effects on endoreduplication via expression in the embryo. The QTLs detected display strong dominance or over-dominance and interacted epistatically with an embryo-expressed QTL. This helps to explain the genetic basis for transgressive segregation in the backcross progeny. Although the favorable alleles that increase mean ploidy and percentage of endoreduplicated nuclei can be contributed by both parents, the Mo17-derived alleles for endoreduplication were often dominant or over-dominant to the Sg18-derived allele. One QTL on chromosome 7 that may be expressed in both the embryo and endosperm exerted a pleiotropic effect on two different parameters of endoreduplication. The results from this study shed light on the regulation of endoreduplication in maize endosperm and provide a marker-assisted selection strategy for potentially improving grain yield.

CPR5 is involved in cell proliferation and cell death control and encodes a novel transmembrane protein

Plants often respond to pathogens by sacrificing cells at the infection site. This type of programmed cell death is mimicked by the constitutive pathogene response5 (cpr5) mutant in Arabidopsis in the absence of pathogens, suggesting a role for CPR5 in programmed cell death control [1]. The analysis of the cellular phenotypes of two T-DNA-tagged cpr5 alleles revealed an additional role for CPR5 in the regulation of endoreduplication and cell division. In cpr5 mutant trichomes, endoreduplication cycles stop after two rounds instead of four, and trichome cells have fewer branches than normal. Eventually, cpr5 trichomes die, the nucleus disintegrates, and the cell collapses. Similarly, leaf growth stops earlier than in wild-type, and, frequently, regions displaying spontaneous cell death are observed. The cloning of the CPR5 gene revealed a novel putative transmembrane protein with a cytosolic domain containing a nuclear-targeting sequence. The dual role of CPR5 in cell proliferation and cell death control suggests a regulatory link between these two processes.

Regulation of endoreduplication in maize (Zea mays L.) endosperm. Isolation of a novel B1-type cyclin and its quantitative analysis.

To investigate the involvement of cyclin in mitotic and endoreduplicative cell cycle control, we have isolated a mitotic cyclin clone from a maize endosperm cDNA library. The deduced amino acid sequence of this clone identifies a novel B1-type cyclin with distinctly different sequence in regions with putative involvement in intracellular localization. This cyclin, designated Zeama;CycB 1;3 (CycZme1), was shown by RNA gel blots and quantitative RT-PCR to be specific for tissues engaging in cell proliferation. It accumulated in metaphase-arrested cells and declined rapidly upon release into G1 phase. During the transition from mitosis to endoreduplication in maize endosperm, CycZme1 transcript declined precipitously while transcripts associated with S phase (histone-H3 and PCNA) and multiple phases of the cell cycle (Cdc2, alpha-tubulin) remained at moderate to high levels. We conclude that CycZme1 down-regulation is involved in the cellular transition to endoreduplication.