Nuclear architecture in developmental biology and cell specialisation

2011 ◽  
Vol 23 (1) ◽  
pp. 94 ◽  
Author(s):  
Thomas Cremer ◽  
Valeri Zakhartchenko
Keyword(s):  
Mammalian Species ◽  
Nuclear Architecture ◽  
Histone Variants ◽  
Preimplantation Embryos ◽  
Mammalian Development ◽  
3D Electron Microscopy ◽  
3D Fluorescence Microscopy ◽  
Additional Level ◽  
Species Specific ◽  
Methylation Patterns

Epigenetic changes, including DNA methylation patterns, histone modifications and histone variants, as well as chromatin remodelling play a fundamental role in the regulation of pre‐ and postimplantation mammalian development. Recent studies have indicated that nuclear architecture provides an additional level of regulation, which needs to be explored in order to understand how a fertilised egg is able to develop into a full organism. Studies of 3D preserved nuclei of IVF preimplantation embryos from different mammalian species, such as mouse, rabbit and cow, have demonstrated that nuclear architecture undergoes major changes during early development. Both similarities and species‐specific differences were observed. Nuclear transfer experiments demonstrated changes of nuclear phenotypes, which to some extent reflect changes seen in IVF preimplantation embryos albeit with a different timing compared with IVF embryos. The dynamics of nuclear architecture is further substantiated by major changes during postmitotic terminal cell differentiation. Recent breakthroughs of 3D fluorescence microscopy with resolution beyond the conventional Abbe limit in combination with 3D electron microscopy provide the potential to explore the topography of nuclear structure with unprecedented resolution and detail.

scholarly journals Heterochromatin Morphodynamics in Late Oogenesis and Early Embryogenesis of Mammals

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1497 ◽  
Author(s):  
Irina Bogolyubova ◽  
Dmitry Bogolyubov
Keyword(s):  
Molecular Mechanisms ◽  
Chromatin Condensation ◽  
Mammalian Species ◽  
Biological Significance ◽  
Histone Variants ◽  
Nuclear Bodies ◽  
Mammalian Development ◽  
Oocyte Growth ◽  
Early Embryos ◽  
Early Mammalian Development

During the period of oocyte growth, chromatin undergoes global rearrangements at both morphological and molecular levels. An intriguing feature of oogenesis in some mammalian species is the formation of a heterochromatin ring-shaped structure, called the karyosphere or surrounded “nucleolus”, which is associated with the periphery of the nucleolus-like bodies (NLBs). Morphologically similar heterochromatin structures also form around the nucleolus-precursor bodies (NPBs) in zygotes and persist for several first cleavage divisions in blastomeres. Despite recent progress in our understanding the regulation of gene silencing/expression during early mammalian development, as well as the molecular mechanisms that underlie chromatin condensation and heterochromatin structure, the biological significance of the karyosphere and its counterparts in early embryos is still elusive. We pay attention to both the changes of heterochromatin morphology and to the molecular mechanisms that can affect the configuration and functional activity of chromatin. We briefly discuss how DNA methylation, post-translational histone modifications, alternative histone variants, and some chromatin-associated non-histone proteins may be involved in the formation of peculiar heterochromatin structures intimately associated with NLBs and NPBs, the unique nuclear bodies of oocytes and early embryos.

scholarly journals FGF/ERK signaling pathway: how it operates in mammalian preimplantation embryos and embryo-derived stem cells

2019 ◽  
Vol 63 (3-4-5) ◽  
pp. 171-186 ◽  
Author(s):  
Anna Soszyńska ◽  
Katarzyna Klimczewska ◽  
Aneta Suwińska
Keyword(s):  
Stem Cells ◽  
Current Knowledge ◽  
Mammalian Species ◽  
Preimplantation Embryos ◽  
Mammalian Development ◽  
Mammalian Embryo ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signals ◽  
Extracellular Signal

The integration of extracellular signals and lineage-specific transcription factors allows cells to react flexibly to their environment, thus endowing the mammalian embryo with the capacity of regulative development. The combination of genetic and pharmacological tools allowing disruption of the fibroblast growth factor / extracellular signal-regulated kinase (FGF/ERK) pathway, together with animal models expressing lineage-specific reporters provided new insights into the role of this signaling cascade during mammalian development, as well as in embryo-derived stem cells. Here, we combine current knowledge acquired from different mammalian models to consider the universality of this cascade in specifying cellular fate across mammalian species.

scholarly journals Modeling human brain tumours in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets

2020 ◽  
Author(s):  
Uswa Shahzad ◽  
Michael S Taccone ◽  
Sachin A Kumar ◽  
Hidehiro Okura ◽  
Stacey Krumholtz ◽  
...  
Keyword(s):  
Brain Tumours ◽  
Mammalian Species ◽  
Scientific Investigation ◽  
Screening Tools ◽  
Murine Models ◽  
Molecular Processes ◽  
C Elegans ◽  
Human Brain Tumours ◽  
Species Specific ◽  
Cancer Studies

Abstract For decades, cell biologists and cancer researchers have taken advantage of non-murine species to increase our understanding of the molecular processes that drive normal cell and tissue development, and when perturbed, cause cancer. The advent of whole genome sequencing has revealed the high genetic homology of these organisms to humans. Seminal studies in non-murine organisms such as D. melanogaster, C. elegans, and D. rerio identified many of the signaling pathways involved in cancer. Studies in these organisms offer distinct advantages over mammalian cell or murine systems. Compared to murine models, these three species have shorter lifespans, are less resource intense, and are amenable to high-throughput drug and RNA interference screening to test a myriad of promising drugs against novel targets. In this review, we introduce species specific breeding strategies, highlight the advantages of modeling brain tumours in each non-mammalian species, and underscore the successes attributed to scientific investigation using these models. We conclude with an optimistic proposal that discoveries in the fields of cancer research, and in particular neuro-oncology, may be expedited using these powerful screening tools and strategies.

Profile of a mammalian sperm receptor

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 1-17 ◽  
Author(s):  
P.M. Wassarman
Keyword(s):  
Gene Expression ◽  
Zona Pellucida ◽  
Specific Gene ◽  
Mammalian Development ◽  
Unique Nature ◽  
Mammalian Fertilization ◽  
Species Specific ◽  
Available Information ◽  
Mammalian Eggs ◽  
Sperm Receptor

Complementary molecules on the surface of eggs and sperm are responsible for species-specific interactions between gametes during fertilization in both plants and animals. In this essay, several aspects of current research on the mouse egg receptor for sperm, a zona pellucida glycoprotein called ZP3, are addressed. These include the structure, synthesis, and functions of the sperm receptor during oogenesis and fertilization in mice. Several conclusions are drawn from available information. These include (I) ZP3 is a member of a unique class of glycoproteins found exclusively in the extracellular coat (zona pellucida) of mammalian eggs. (II) ZP3 gene expression is an example of oocyte-specific and, therefore, sex-specific gene expression during mammalian development. (III) ZP3 is a structural glycoprotein involved in assembly of the egg extracellular coat during mammalian oogenesis. (IV) ZP3 is a sperm receptor involved in carbohydrate-mediated gamete recognition and adhesion during mammalian fertilization. (V) ZP3 is an inducer of sperm exocytosis (acrosome reaction) during mammalian fertilization. (VI) ZP3 participates in the secondary block to polyspermy following fertilization in mammals. (VII) The extracellular coat of other mammalian eggs contains a glycoprotein that is functionally analogous to mouse ZP3. The unique nature, highly restricted expression, and multiple roles of ZP3 during mammalian development make this glycoprotein a particularly attractive subject for investigation at both the cellular and molecular levels.

Evolutionary origin of the cell nucleus and its functional architecture

2010 ◽  
Vol 48 ◽  
pp. 1-24 ◽  
Author(s):  
Jan Postberg ◽  
Hans J. Lipps ◽  
Thomas Cremer
Keyword(s):  
Cell Nucleus ◽  
Interdisciplinary Research ◽  
Nuclear Organization ◽  
Nuclear Architecture ◽  
Evolutionary Origin ◽  
Cell Type ◽  
Research Strategies ◽  
Evolutionarily Conserved ◽  
Species Specific ◽  
The Impact

Understanding the evolutionary origin of the nucleus and its compartmentalized architecture provides a huge but, as expected, greatly rewarding challenge in the post-genomic era. We start this chapter with a survey of current hypotheses on the evolutionary origin of the cell nucleus. Thereafter, we provide an overview of evolutionarily conserved features of chromatin organization and arrangements, as well as topographical aspects of DNA replication and transcription, followed by a brief introduction of current models of nuclear architecture. In addition to features which may possibly apply to all eukaryotes, the evolutionary plasticity of higher-order nuclear organization is reflected by cell-type- and species-specific features, by the ability of nuclear architecture to adapt to specific environmental demands, as well as by the impact of aberrant nuclear organization on senescence and human disease. We conclude this chapter with a reflection on the necessity of interdisciplinary research strategies to map epigenomes in space and time.

Transcription factor AP-2γ is essential in the extra-embryonic lineages for early postimplantation development

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2733-2747 ◽  
Author(s):  
Heidi J. Auman ◽  
Timothy Nottoli ◽  
Olga Lakiza ◽  
Quinton Winger ◽  
Stephanie Donaldson ◽  
...  
Keyword(s):  
Mouse Genome Informatics ◽  
Preimplantation Embryos ◽  
Mammalian Development ◽  
Placental Development ◽  
Specific Expression ◽  
Stem Cell Maintenance ◽  
Embryonic Tissues ◽  
Trophoblast Stem Cell ◽  
Deficient Mice ◽  
Anterior Posterior

The members of the AP-2 family of transcription factors play important roles during mammalian development and morphogenesis. AP-2γ (Tcfap2c – Mouse Genome Informatics) is a retinoic acid-responsive gene implicated in placental development and the progression of human breast cancer. We show that AP-2γ is present in all cells of preimplantation embryos and becomes restricted to the extra-embryonic lineages at the time of implantation. To study further the biological function of AP-2γ, we have generated Tcfap2c-deficient mice by gene disruption. The majority of Tcfap2c–/– mice failed to survive beyond 8.5 days post coitum (d.p.c.). At 7.5 d.p.c., Tcfap2c–/– mutants were typically arrested or retarded in their embryonic development in comparison to controls. Morphological and molecular analyses of mutants revealed that gastrulation could be initiated and that anterior-posterior patterning of the epiblast remained intact. However, the Tcfap2c mutants failed to establish a normal maternal-embryonic interface, and the extra-embryonic tissues were malformed. Moreover, the trophoblast-specific expression of eomesodermin and Cdx2, two genes implicated in FGF-responsive trophoblast stem cell maintenance, was significantly reduced. Chimera studies demonstrated that AP-2γ plays no major autonomous role in the development of the embryo proper. By contrast, the presence of AP-2γ in the extra-embryonic membranes is required for normal development of this compartment and also for survival of the mouse embryo.

Aging, cellular senescence and cancer: epigenetic alterations and nuclear remodeling

2019 ◽  
pp. 238-253
Author(s):  
John C. Lucchesi
Keyword(s):  
Histone Modifications ◽  
Cellular Senescence ◽  
Aging Process ◽  
Nuclear Architecture ◽  
Gene Mutations ◽  
Histone Variants ◽  
Premature Aging ◽  
Model Organisms ◽  
Premature Aging Syndromes ◽  
Nuclear Remodeling

Epigenetic modifications correlated with aging and oncogenesis are changes in the pattern of DNA methylation and of histone modifications, and changes in the level of histone variants (H3.3, macroH2A, H2A.Z) and gene mutations. The sirtuins are a set of highly conserved protein deacetylases of particular significance to the aging process. Many cancer types are found to carry mutations in chromatin-modifying genes such as those encoding methyl or acetyl transferases, affecting the histone modifications of promoters and enhancers. The aging process and oncogenesis present a number of changes in the nuclear architecture. Mutations in the lamina-coding genes lead to premature aging syndromes. Mutations in remodeling complexes are found in different cancers. Modifications that affect the architectural protein binding sites at topologically associating domain (TAD) borders can cause the merging of neighboring TADs. The levels of short non-coding RNAs (sncRNAs) are altered in model organisms and are associated with cancer. Changes in the position of chromosome territories often occur in tumor cells. Nevertheless, cellular senescence, due mostly to the absence of telomerase, represents a mechanism of tumor suppression.

scholarly journals Lipid Stores and Lipid Metabolism Associated Gene Expression in Porcine and Bovine Parthenogenetic Embryos Revealed by Fluorescent Staining and RNA-seq

2020 ◽  
Vol 21 (18) ◽  
pp. 6488
Author(s):  
Arkadiusz Kajdasz ◽  
Ewelina Warzych ◽  
Natalia Derebecka ◽  
Zofia E. Madeja ◽  
Dorota Lechniak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Inner Cell Mass ◽  
Mammalian Species ◽  
Cell Mass ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Bovine Blastocyst

Compared to other mammalian species, porcine oocytes and embryos are characterized by large amounts of lipids stored mainly in the form of droplets in the cytoplasm. The amount and the morphology of lipid droplets (LD) change throughout the preimplantation development, however, relatively little is known about expression of genes involved in lipid metabolism of early embryos. We compared porcine and bovine blastocyst stage embryos as well as dissected inner cell mass (ICM) and trophoblast (TE) cell populations with regard to lipid droplet storage and expression of genes functionally annotated to selected lipid gene ontology terms using RNA-seq. Comparing the number and the volume occupied by LD between bovine and porcine blastocysts, we have found significant differences both at the level of single embryo and a single blastomere. Aside from different lipid content, we found that embryos regulate the lipid metabolism differentially at the gene expression level. Out of 125 genes, we found 73 to be differentially expressed between entire porcine and bovine blastocyst, and 36 and 51 to be divergent between ICM and TE cell lines. We noticed significant involvement of cholesterol and ganglioside metabolism in preimplantation embryos, as well as a possible shift towards glucose, rather than pyruvate dependence in bovine embryos. A number of genes like DGAT1, CD36 or NR1H3 may serve as lipid associated markers indicating distinct regulatory mechanisms, while upregulated PLIN2, APOA1, SOAT1 indicate significant function during blastocyst formation and cell differentiation in both models.

258. Differential expression of H2A and H3 variant histones in mouse preimplantation embryos and R1 ES cells

2008 ◽  
Vol 20 (9) ◽  
pp. 58
Author(s):  
G. R. Kafer ◽  
SA Lehnert ◽  
P. L. Kaye ◽  
R. J. Moser
Keyword(s):  
Messenger Rna ◽  
Expression Profiles ◽  
Es Cells ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Histone Variants ◽  
Histone Variant ◽  
Preimplantation Embryos ◽  
Es Cell

Histone variants replace canonical histones in nucleosomes to serve numerous biological processes. This integration alters DNA properties to ultimately regulate gene expression. Previous mouse studies have indicated that some variants (H2AZ and H3.3) are essential for survival, but here we document and correlate histone expression patterns with key developmental events. Using quantitative reverse-transcribed PCR (qRT–PCR) we investigated the expression of 7 genes coding for H2A variants and 4 genes coding for H3 variants in mouse preimplantation embryos and in pluripotent R1 ES cells. Messenger RNA was extracted from pools of 3 embryos flushed from superovulated mice. Embryos were collected at five stages, zygotes, 2-cell embryos, morulae, blastocysts and hatching blastocysts (20 h, 44 h, 68 h, 92 h and 116 h post hCG respectively). The expression of H2A variant genes typically peaked within blastocysts. H2AZ and H2AX expression was 80 – 95% higher in blastocysts than other stages. Conversely, genes coding for H3 variants showed elevated expression in zygotes, where H3.3 expression was 85 – 95% higher and CENPA was ~75% higher than in later preimplantation stages. The expression profiles of histone remodellers SWI/SNF and CAF-1 correlated with the variants they are known to remodel (H2A and H3 variants respectively), suggesting an increased integration of those variants into nucleosomes. We also compared blastocyst and embryonic stem cell (ES cell) expression patterns. R1 ES cells express all histone variants, including H2A.Bbd, H3.1 and H3.2 which were not expressed in preimplantation embryos. Further, expression levels of every histone variant investigated differed significantly between R1 ES cells and hatching blastocysts (ANOVA, P < 0.05, n = 3 experiments). We conclude that histone variant expression reflects preimplantation developmental demands. Further, histone code expression profiles show significant change upon extended cell culture and maintenance of pluripotency as indicated by comparing in vivo hatching blastocysts to the R1 ES cell line.

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