17 research outputs found
Two mosaic terminal inverted duplications arising post-zygotically: Evidence for possible formation of neo-telomeres
A Complex Cell Division Machinery Was Present in the Last Common Ancestor of Eukaryotes
Background: The midbody is a transient complex structure containing proteins involved in cytokinesis. Up to now, it has been described only in Metazoa. Other eukaryotes present a variety of structures implied in the last steps of cell division, such as the septum in fungi or the phragmoplast in plants. However, it is unclear whether these structures are homologous (derive from a common ancestral structure) or analogous (have distinct evolutionary origins). Recently, the proteome of the hamster midbody has been characterized and 160 proteins identified. Methodology/Principal Findings: Using phylogenomic approaches, we show here that nearly all of these 160 proteins (95%) are conserved across metazoan lineages. More surprisingly, we show that a large part of the mammalian midbody components (91 proteins) were already present in the last common ancestor of all eukaryotes (LECA) and were most likely involved in the construction of a complex multi-protein assemblage acting in cell division. Conclusions/Significance: Our results indicate that the midbodies of non-mammalian metazoa are likely very similar to the mammalian one and that the ancestor of Metazoa possessed a nearly modern midbody. Moreover, our analyses support the hypothesis that the midbody and the structures involved in cytokinesis in other eukaryotes derive from a large and complex structure present in LECA, likely involved in cytokinesis. This is an additional argument in favour of the idea of a comple
There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator
HΓΆhn S, Hallmann A. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator. BMC Biology. 2011;9(1): 89.Background:
Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out?
Results:
In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri.
Conclusions:
Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator
An Osmotic Model of the Growing Pollen Tube
Pollen tube growth is central to the sexual reproduction of plants and is a longstanding model for cellular tip growth. For rapid tip growth, cell wall deposition and hardening must balance the rate of osmotic water uptake, and this involves the control of turgor pressure. Pressure contributes directly to both the driving force for water entry and tip expansion causing thinning of wall material. Understanding tip growth requires an analysis of the coordination of these processes and their regulation. Here we develop a quantitative physiological model which includes water entry by osmosis, the incorporation of cell wall material and the spreading of that material as a film at the tip. Parameters of the model have been determined from the literature and from measurements, by light, confocal and electron microscopy, together with results from experiments made on dye entry and plasmolysis in Lilium longiflorum. The model yields values of variables such as osmotic and turgor pressure, growth rates and wall thickness. The model and its predictive capacity were tested by comparing programmed simulations with experimental observations following perturbations of the growth medium. The model explains the role of turgor pressure and its observed constancy during oscillations; the stability of wall thickness under different conditions, without which the cell would burst; and some surprising properties such as the need for restricting osmotic permeability to a constant area near the tip, which was experimentally confirmed. To achieve both constancy of pressure and wall thickness under the range of conditions observed in steady-state growth the model reveals the need for a sensor that detects the driving potential for water entry and controls the deposition rate of wall material at the tip
Oxaliplatin and cisplatin cause similar chromosomal changes in H69 SCLC cells: linking changes in genotype to the resistant phenotype
Chromosomal rearrangement has been studied in drug resistant cancer cell lines and in tumour samples from cancer patients. Many rearrangements have been observed, however what is less clear is the relationship between these rearrangements and the drug resistant phenotype. Are these changes in karyotype the cause of the drug resistance or are they a side effect of exposure to DNA targeted chemotherapeutics and not directly responsible for the resistance? We have developed a clinically relevant model of low level cisplatin and oxaliplatin resistance in human H69 small cell lung cancer cells. These cells are stably 2-fold resistant to both platinum drugs for 8 weeks in drug free culture, then they revert to a non-resistant phenotype. We have performed an Affymetrix 10K SNP Array and cytogenetic analysis to characterise the chromosomal changes in these resistant cell lines. Many chromosomal differences were found between the parental and resistant cell lines. The largest rearrangement associated with the development of platinum drug resistance was on chromosome 6, where both cisplatin and oxaliplatin have independently caused similar chromosomal breakages at 6q21 and a decrease in copy number distal to this breakpoint. This may indicate the presence of tumour suppressor genes between 6q21-qter. Other changes in common between the two drug resistant cell lines include +21 and -13pter-13q.14.11. The oxaliplatin resistant cell line had a greater number of minor changes including losses from the p arm of the X chromosome. Examining the chromosomal differences again after the loss of resistance should make clear which rearrangements are associated with the drug resistance phenotype and which are a by-product of the development of resistance. We have also compared our data from the Affymetrix array, to mRNA expression of 1000 genes associated with the stress response to chemotherapeutics and found no association for this subset of genes. This paper presents for the first time a DNA array and cytogenetic profile of the H69 small cell lung cancer cell line which harbours a large c-myc amplification. This is also the first cytogenetic analysis of an oxaliplatin resistant cell line
JRK is a positive regulator of Ξ²-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.
The loss of Ξ²-catenin inhibitory components is a well-established mechanism of carcinogenesis but Ξ²-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the Ξ²-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a Ξ²-catenin activator function, depletion of JRK in several cancer cell lines repressed Ξ²-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of Ξ²-catenin target genes and increased cell proliferation. This study shows that JRK is required for Ξ²-catenin hyperactivity regardless of the adenomatous polyposis coli/Ξ²-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer
JRK is a positive regulator of Ξ²-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer
The loss of Ξ²-catenin inhibitory components is a well-established mechanism of carcinogenesis but Ξ²-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the Ξ²-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a Ξ²-catenin activator function, depletion of JRK in several cancer cell lines repressed Ξ²-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of Ξ²-catenin target genes and increased cell proliferation. This study shows that JRK is required for Ξ²-catenin hyperactivity regardless of the adenomatous polyposis coli/Ξ²-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer
Supplementary Material for:A Paediatric Acute Promyelocytic Leukaemia Patient Harbouring a Cryptic PML-RARA Insertion due to a Complex Structural Chromosome 17 Rearrangement
Acute promyelocytic leukaemia with <i>PML-RARA</i> fusion is usually associated with the t(15;17)(q24.1;q21.1) translocation but may also arise from complex or cryptic rearrangements. The fusion usually resides on chromosome 15 but occasionally on others. We describe a cryptic <i>PML-RARA </i>fusion within a novel chromosome 17 rearrangement. We performed interphase fluorescence in situ hybridisation (FISH) using a dual-fusion <i>PML-RARA </i>probe, followed by reverse transcriptase-polymerase chain reaction (RT-PCR) for <i>PML-RARA</i>, karyotyping, and metaphase FISH using <i>RARA</i>break-apart, locus-specific, and subtelomere probes for chromosome 17. An 850K SNP microarray was also employed. Interphase and metaphase FISH showed atypical results involving a single <i>PML</i>-<i>RARA</i> fusion, no second fusion, but instead separate diminished <i>PML</i> and <i>RARA</i> signals. RT-PCR confirmed <i>PML-RARA </i>fusion; however, karyotyping detected only an altered chromosome 17. Metaphase FISH showed the single fusion and diminished 5β²<i> RARA</i> signals located unexpectedly in the subtelomeric short-arm and long-arm regions of the rearranged chromosome 17, respectively. SNP microarray revealed no copy number abnormality. This paediatric patient with <i>PML-RARA</i> fusion reflects a cryptic insertion that resides within a complex and novel chromosome 17 rearrangement. This rearrangement likely arose via 7 chromosome breaks with the insertion occurring first followed by sequential paracentric and then pericentric inversions
Chromosomal Rearrangements and Novel Genes in Disorders of Eye Development, Cataract and Glaucoma
Charophyceae (charales)
The charophytes, or stoneworts, are a group of green algae with six extant genera in one family, distributed worldwide in freshwater ponds and lakes. They are among the green algal groups most closely related to land plants and exhibit a complex thallus, with multinucleate internodal cells joined at nodes comprising smaller, uninucleate cells giving rise to whorled branchlets. Two genera (Chara, Nitella) contain most of the described species, with a third (Tolypella) containing several dozen taxa. The remaining genera have one or a few species. Reproduction is oogamous, with sperm and eggs produced in separate multicellular structures. The thallus is haploid; the zygote is the only diploid cell in the life cycle, and meiosis is followed by the development of a resistant spore. Thalli and spores are often encrusted with calcium carbonate. Such spores are abundant in the fossil record of the Charales, which extends to the Upper Silurian, and many genera and families have become extinct. These algae provide important ecosystem services, for example, as colonizing species, as biological agents for producing water clarity, or as the base of the food web. Charophytes are important for the study of evolution of embryophyte development, growth meristems, and cell biophysics. As one of the green algal groups most closely related to land plants, the rich charophyte fossil record may reveal clues regarding the earliest algae that invaded the land