The Experts below are selected from a list of 28572 Experts worldwide ranked by ideXlab platform
Heide Schatten - One of the best experts on this subject based on the ideXlab platform.
-
the role of Centrosomes in fertilization cell division and establishment of asymmetry during embryo development
Seminars in Cell & Developmental Biology, 2010Co-Authors: Heide SchattenAbstract:Centrosomes play significant central roles during reproduction, cell division, embryo development and stem cell biology, and a wealth of new information has been accumulated during the past decade that spans molecular details and newly discovered functions/dysfunctions for specific Centrosome proteins in various cellular activities. The present review will focus on the current state of knowledge on the role of germ cell Centrosomes during fertilization, formation of the zygote Centrosome, Centrosome duplication and separation during first embryonic cell division, and asymmetric cell divisions during cell differentiation and subsequent embryo development. It will also address asymmetric cell division in stem cells and formation of the primary cilium during embryo development.
-
the functional significance of Centrosomes in mammalian meiosis fertilization development nuclear transfer and stem cell differentiation
Environmental and Molecular Mutagenesis, 2009Co-Authors: Heide SchattenAbstract:Centrosomes had been discovered in germ cells and germ cells continue to provide excellent but also challenging material in which to study complex centrosomal dynamics. The present review highlights the importance of Centrosomes for meiotic spindle integrity and the susceptibility of meiotic spindle Centrosomes to aging and drugs or toxic agents which may be associated with female infertility, aneuploidy, and developmental abnormalities. We discuss cell and molecular aspects of Centrosomes during fertilization, a critical stage in which Centrosomes play crucial roles in precisely organizing the sperm aster that allows apposition of male and female genomes followed by formation of the zygote aster that is important for the formation of the bipolar spindle apparatus during cell division. Development of an embryo involves sequential cell divisions in which Centrosomes play a critical role in establishing asymmetry that allows differentiation of cells and targeted signal transductions for the developing embryo. Asymmetric Centrosome dynamics are also critical for stem cell division to maintain one daughter cell as a stem cell while the other daughter cell undergoes Centrosome growth in preparation for differentiation. This review also discusses the complex interactions of somatic cell Centrosomes with the recipient oocyte in reconstructed (cloned) embryos in which Centrosome remodeling is crucial to fulfill functions that are carried out by the zygote Centrosome in fertilized eggs. We close our discussion with a look at Centrosome dysfunctions and implications for male fertility and assisted reproduction. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc.
-
the role of Centrosomes in mammalian fertilization and its significance for icsi
Molecular Human Reproduction, 2009Co-Authors: Heide SchattenAbstract:Centrosome integrity is critically important for successful fertilization and embryo development. In humans, the sperm contributes the dominant centrosomal material containing centrioles and centrosomal components onto which oocyte centrosomal proteins assemble after sperm incorporation to form the sperm aster that is essential for uniting sperm and oocyte pronuclei. Increasingly, dysfunctional sperm Centrosomes have been identified as a factor for sperm-derived infertility and heterologous Intracytoplasmic Sperm Injection (ICSI) has been used to assess Centrosome and sperm aster formation and clearly established a relationship between infertility and sperm centrosomal dysfunction. ICSI has been used successfully to provide novel treatment to overcome male factor infertility and it may open up new possibilities to correct specific sperm-related Centrosome dysfunctions at molecular levels. New data indicate that it is now possible to replace dysfunctional Centrosomes with functional donor sperm Centrosomes which may provide new treatment for couples in which infertility is a result of Centrosome-related sperm dysfunctions.
-
The mammalian Centrosome and its functional significance
Histochemistry and Cell Biology, 2008Co-Authors: Heide SchattenAbstract:Primarily known for its role as major microtubule organizing center, the Centrosome is increasingly being recognized for its functional significance in key cell cycle regulating events. We are now at the beginning of understanding the Centrosome’s functional complexities and its major impact on directing complex interactions and signal transduction cascades important for cell cycle regulation. The Centrosome orchestrates entry into mitosis, anaphase onset, cytokinesis, G1/S transition, and monitors DNA damage. Recently, the Centrosome has also been recognized as major docking station where regulatory complexes accumulate including kinases and phosphatases as well as numerous other cell cycle regulators that utilize the Centrosome as platform to coordinate multiple cell cycle-specific functions. Vesicles that are translocated along microtubules to and away from Centrosomes may also carry enzymes or substrates that use Centrosomes as main docking station. The Centrosome’s role in various diseases has been recognized and a wealth of data has been accumulated linking dysfunctional Centrosomes to cancer, Alstrom syndrome, various neurological disorders, and others. Centrosome abnormalities and dysfunctions have been associated with several types of infertility. The present review highlights the Centrosome’s significant roles in cell cycle events in somatic and reproductive cells and discusses Centrosome abnormalities and implications in disease.
Hongguo Yu - One of the best experts on this subject based on the ideXlab platform.
-
is cohesin required for spindle pole body Centrosome cohesion
Communicative & Integrative Biology, 2012Co-Authors: Martin Avey, Hongguo YuAbstract:Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the Centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal Centrosome. The parental Centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated Centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal Centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with Centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in Centrosome regulation appears to be indirect in budding yeast.
-
Is cohesin required for spindle-pole-body/Centrosome cohesion?
Communicative & Integrative Biology, 2012Co-Authors: Martin Avey, Hongguo YuAbstract:Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the Centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal Centrosome. The parental Centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated Centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal Centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with Centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in Centrosome regulation appears to be indirect in budding yeast.
Kenji Fukasawa - One of the best experts on this subject based on the ideXlab platform.
-
Suppression of Centrosome duplication and amplification by deacetylases.
Cell Cycle, 2012Co-Authors: Hongbo Ling, Lirong Peng, Edward Seto, Kenji FukasawaAbstract:Centrosome duplication is controlled both negatively and positively by a number of proteins. The activities and stabilities of those regulatory proteins are in many cases controlled by posttranslational modifications. Although acetylation and deacetylation are highly common posttranslational modifications, their roles in the regulation of Centrosome duplication had not been closely examined. Here, through focusing on the deacetylases, we investigated the role of acetylation/deacetylation in the regulation of Centrosome duplication and induction of abnormal amplification of Centrosomes. We found that the deacetylation event negatively controls Centrosome duplication and amplification. Of the 18 total known deacetylases (HDAC1-11, SIRT1-7), ten deacetylases possess the activity to suppress Centrosome amplification, and their Centrosome amplification suppressing activities are strongly associated with their abilities to localize to Centrosomes. Among them, HDAC1, HDAC5 and SIRT1 show the highest suppressing activities, but each of them suppresses Centrosome duplication and/or amplification with its unique mechanism.
-
Aberrant Activation of Cell Cycle Regulators, Centrosome Amplification, and Mitotic Defects
Hormones and Cancer, 2011Co-Authors: Kenji FukasawaAbstract:The Centrosome that functions as a microtubule organizing center of a cell plays a key role in formation of bipolar mitotic spindles. Cells normally have either one (unduplicated) or two (duplicated) Centrosomes. However, loss of the mechanisms controlling the numeral integrity of Centrosomes leads to Centrosome amplification (presence of more than two Centrosomes), primarily via overduplication or fragmentation of Centrosomes, resulting in defective mitosis and consequentially chromosome instability. Centrosome amplification frequently occurs in various cancers, and is considered as a major cause of chromosome instability. It has recently been found that ROCK2 kinase plays a critical role in promotion of Centrosome duplication and amplification. Considering that ROCK2 is activated by Rho protein, and Rho is the immediate downstream target of many growth and hormone receptors, it is possible that such receptors may rather directly affect Centrosome duplication and amplification. Indeed, constitutive activation of the receptors known to signal to the Rho pathway leads to promotion of Centrosome amplification and chromosome instability in the Rho-ROCK2 pathway-dependent manner. These observations reveal an unexplored, yet important, oncogenic activities of those receptors in carcinogenesis; destabilizing chromosomes through promotion of Centrosome amplification via continual activation of the Rho-ROCK2 pathway.
-
p53 cyclin dependent kinase and abnormal amplification of Centrosomes
Biochimica et Biophysica Acta, 2008Co-Authors: Kenji FukasawaAbstract:Centrosomes play a critical role in formation of bipolar mitotic spindles, an essential event for accurate chromosome segregation into daughter cells. Numeral abnormalities of Centrosomes (Centrosome amplification) occur frequently in cancers, and are considered to be the major cause of chromosome instability, which accelerates acquisition of malignant phenotypes during tumor progression. Loss or mutational inactivation of p53 tumor suppressor protein, one of the most common mutations found in cancers, results in a high frequency of Centrosome amplification in part via allowing the activation of the cyclin-dependent kinase (CDK) 2-cyclin E (as well as CDK2-cyclin A) which is a key factor for the initiation of Centrosome duplication. In this review, the role of Centrosome amplification in tumor progression, and mechanistic view of how Centrosomes are amplified in cells through focusing on loss of p53 and aberrant activities of CDK2-cyclins will be discussed.
-
Oncogenes and tumour suppressors take on Centrosomes
Nature Reviews Cancer, 2007Co-Authors: Kenji FukasawaAbstract:Centrosomes have a crucial role in the formation of bipolar mitotic spindles, which are essential for accurate chromosome segregation. Certain oncogenic and tumour-suppressor proteins control Centrosome duplication and function. How does their mutation result in numeral and functional Centrosome abnormalities? Chromosome instability, which is equated to mitotic defects and consequential chromosome segregation errors, provides a formidable basis for the acquisition of further malignant phenotypes during tumour progression. Centrosomes have a crucial role in the formation of bipolar mitotic spindles, which are essential for accurate chromosome segregation. Mutations of certain oncogenic and tumour-suppressor proteins directly induce chromosome instability by disrupting the normal function and numeral integrity of Centrosomes. How these proteins control Centrosome duplication and function, and how their mutational activation and/or inactivation results in numeral and functional Centrosome abnormalities, is discussed in this Review. As core components of spindle poles, Centrosomes have a key role in directing the formation of bipolar mitotic spindles, which is crucial for accurate segregation of chromosomes during cytokinesis. Numeral and functional abnormalities of Centrosomes result in mitotic spindle defects, leading to chromosome segregation errors, and are the major causes of chromosome instability in cancer, which accelerates the step-wise tumour progression. Several oncogenic and tumour-suppressor proteins are found to be involved in the regulation of Centrosome duplication and function, and mutations of those proteins result in mitotic defects that are associated with numeral and functional abnormalities of Centrosomes. The Centrosome regulation activities of these oncogenic and tumour-suppressor proteins are crucial parts of their overall oncogenic, tumour-suppressing potential.
-
Centrosome amplification chromosome instability and cancer development
Cancer Letters, 2005Co-Authors: Kenji FukasawaAbstract:During mitosis, two Centrosomes form spindle poles and direct the formation of bipolar mitotic spindles, which is an essential event for accurate chromosome segregation into daughter cells. The presence of more than two Centrosomes (Centrosome amplification), severely disturbs mitotic process and cytokinesis via formation of more than two spindle poles, resulting in an increased frequency of chromosome segregation errors (chromosome instability). Destabilization of chromosomes by Centrosome amplification aids acquisition of further malignant phenotypes, hence promoting tumor progression. Centrosome amplification occurs frequently in almost all types of cancer, and is considered as the major contributing factor for chromosome instability in cancer cells. Upon cytokinesis, each daughter cell receives one Centrosome, and thus Centrosome must duplicate once, and only once, before the next mitosis. If Centrosomes duplicate more than once within a single cell cycle, Centrosome amplification occurs, which is frequently seen in cells harboring mutations in some tumor suppressor proteins such as p53 and BRCA1. The recent studies have provided critical information for understanding how loss of these proteins allows multiple rounds of Centrosome duplication. In this review, how Centrosome amplification destabilizes chromosomes, how loss of certain tumor suppressor proteins leads to Centrosome amplification, and the role of Centrosome amplification in cancer development will be discussed.
Martin Avey - One of the best experts on this subject based on the ideXlab platform.
-
is cohesin required for spindle pole body Centrosome cohesion
Communicative & Integrative Biology, 2012Co-Authors: Martin Avey, Hongguo YuAbstract:Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the Centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal Centrosome. The parental Centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated Centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal Centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with Centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in Centrosome regulation appears to be indirect in budding yeast.
-
Is cohesin required for spindle-pole-body/Centrosome cohesion?
Communicative & Integrative Biology, 2012Co-Authors: Martin Avey, Hongguo YuAbstract:Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the Centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal Centrosome. The parental Centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated Centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal Centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with Centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in Centrosome regulation appears to be indirect in budding yeast.
Conly L Rieder - One of the best experts on this subject based on the ideXlab platform.
-
Centrosome independent mitotic spindle formation in vertebrates
Current Biology, 2000Co-Authors: Conly L Rieder, Alexey Khodjakov, Richard W Cole, Berl R OakleyAbstract:Abstract Background: In cells lacking Centrosomes, the microtubule-organizing activity of the Centrosome is substituted for by the combined action of chromatin and molecular motors. The question of whether a Centrosome-independent pathway for spindle formation exists in vertebrate somatic cells, which always contain Centrosomes, remains unanswered, however. By a combination of labeling with green fluorescent protein (GFP) and laser microsurgery we have been able to selectively destroy Centrosomes in living mammalian cells as they enter mitosis. Results: We have established a mammalian cell line in which the boundaries of the Centrosome are defined by the constitutive expression of γ-tubulin–GFP. This feature allows us to use laser microsurgery to selectively destroy the Centrosomes in living cells. Here we show that this method can be used to reproducibly ablate the Centrosome as a functional entity, and that after destruction the microtubules associated with the ablated Centrosome disassemble. Depolymerization–repolymerization experiments reveal that microtubules form in acentrosomal cells randomly within the cytoplasm. When both Centrosomes are destroyed during prophase these cells form a functional bipolar spindle. Surprisingly, when just one Centrosome is destroyed, bipolar spindles are also formed that contain one centrosomal and one acentrosomal pole. Both the polar regions in these spindles are well focused and contain the nuclear structural protein NuMA. The acentrosomal pole lacks pericentrin, γ-tubulin, and centrioles, however. Conclusions: These results reveal, for the first time, that somatic cells can use a Centrosome-independent pathway for spindle formation that is normally masked by the presence of the Centrosome. Furthermore, this mechanism is strong enough to drive bipolar spindle assembly even in the presence of a single functional Centrosome.
-
the coordination of Centrosome reproduction with nuclear events of the cell cycle in the sea urchin zygote
Journal of Cell Biology, 1998Co-Authors: Edward H Hinchcliffe, Conly L Rieder, Grizzel O Cassels, Greenfield SluderAbstract:Centrosomes repeatedly reproduce in sea urchin zygotes arrested in S phase, whether cyclin-dependent kinase 1–cyclin B (Cdk1-B) activity remains at prefertilization levels or rises to mitotic values. In contrast, when zygotes are arrested in mitosis using cyclin B Δ-90, anaphase occurs at the normal time, yet Centrosomes do not reproduce. Together, these results reveal the cell cycle stage specificity for Centrosome reproduction and demonstrate that neither the level nor the cycling of Cdk1-B activity coordinate Centrosome reproduction with nuclear events. In addition, the proteolytic events of the metaphase–anaphase transition do not control when Centrosomes duplicate. When we block protein synthesis at first prophase, the zygotes divide and arrest before second S phase. Both blastomeres contain just two complete Centrosomes, which indicates that the cytoplasmic conditions between mitosis and S phase support Centrosome reproduction. However, the fact that these daughter Centrosomes do not reproduce again under such supportive conditions suggests that they are lacking a component required for reproduction. The repeated reproduction of Centrosomes during S phase arrest points to the existence of a necessary “licensing” event that restores this component to daughter Centrosomes during S phase, preparing them to reproduce in the next cell cycle.