The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Fugaku Aoki - One of the best experts on this subject based on the ideXlab platform.
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minor zygotic gene activation is essential for mouse preimplantation development
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Kenichiro Abe, Richard M. Schultz, Satoshi Funaya, Dai Tsukioka, Machika Kawamura, Yutaka Suzuki, Masataka G Suzuki, Fugaku AokiAbstract:In mice, transcription initiates at the mid-one-Cell Stage and transcriptional activity dramatically increases during the two-Cell Stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-Cell Stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-Cell Stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.
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Linker histone H1FOO regulates the chromatin structure in mouse zygotes.
FEBS letters, 2018Co-Authors: Satoshi Funaya, Masataka G Suzuki, Masatoshi Ooga, Fugaku AokiAbstract:The chromatin structure in one-Cell-Stage mouse embryos is extremely loose and becomes tighter at the two-Cell Stage. As linker histones are involved in higher-order chromatin structure, we examined the involvement of the linker histone variant H1foo in the change of chromatin looseness between the one- and two-Cell Stages. H1foo knockdown causes the chromatin structure to be tighter in the pronucleus and increases deposition of the histone H3 variant H3.1/3.2 in the peripheral region of the pronucleus in one-Cell-Stage embryos. The decrease in chromatin looseness at the two-Cell Stage is less after overexpressing H1foo. These results suggest that H1foo is involved in the change in chromatin structure via nuclear deposition of H3 variants between the one- and two-Cell Stages.
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regulation of transketolase like 1 gene expression in the murine one Cell Stage embryos
PLOS ONE, 2014Co-Authors: Go Hamamoto, Masataka G Suzuki, Tsukasa Suzuki, Fugaku AokiAbstract:In mice, transcription from the zygotic genome starts at the mid-one-Cell Stage after fertilization. Previous studies showed that an enhancer is not required for transcription at this Stage, and that the enhancer-dependent mechanism of transcription is established during the two-Cell Stage. However, these results were obtained using reporter gene assays with promoters derived from viruses, rather than from endogenous genes. We conducted a reporter-gene assay using the promoter of Tktl1, which is transcribed after fertilization, to investigate the mechanism regulating gene expression at the one-Cell Stage. When a plasmid containing the 2467 bp upstream and 25 bp downstream of the Tktl1 transcription start site (TSS) was microinjected into the nuclei of growing oocytes, and one-Cell Stage and early and late two-Cell-Stage embryos, transcriptional activity was detected in the one-Cell- and two-Cell-Stage embryos, but not in the oocytes. It was highest at the early two-Cell Stage and was reduced at the late two-Cell Stage. The decrease in activity at the late two-Cell Stage was prevented by inhibiting the second round of DNA replication, suggesting that the transcriptionally repressive state is established during the two-Cell Stage by a mechanism coupled to DNA replication. When the Tktl1 promoter was deleted to leave 56 bp upstream of the TSS which includes GC and TATA boxes, transcriptional activity was still detected in one-Cell-Stage embryos, but not early or late two-Cell-Stage embryos. The core promoter of Tktl1 alone seems to be able to induce basal transcription at the one-Cell Stage. These results suggest that repressive chromatin is established after fertilization in two steps, which occur during the transition from the one- to two-Cell Stage and during DNA replication at the two-Cell Stage.
Richard M. Schultz - One of the best experts on this subject based on the ideXlab platform.
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minor zygotic gene activation is essential for mouse preimplantation development
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Kenichiro Abe, Richard M. Schultz, Satoshi Funaya, Dai Tsukioka, Machika Kawamura, Yutaka Suzuki, Masataka G Suzuki, Fugaku AokiAbstract:In mice, transcription initiates at the mid-one-Cell Stage and transcriptional activity dramatically increases during the two-Cell Stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-Cell Stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-Cell Stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.
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transient expression of translation initiation factor eif 4c during the 2 Cell Stage of the preimplantation mouse embryo identification by mrna differential display and the role of dna replication in zygotic gene activation
Developmental Biology, 1996Co-Authors: Warren Davis, P A De Sousa, Richard M. SchultzAbstract:Zygotic gene activation (ZGA) definitely occurs by the 2-Cell Stage in the mouse embryo. Analysis of protein synthesis by two-dimensional gel electrophoresis reveals a class of genes whose expression transiently increases in the 2-Cell embryo. Although the paucity of biological material has prevented a systematic identification of these genes, the mRNA differential display method circumvents this problem. Using this approach we find a transient increase in the mRNA abundance of the translation initiation factor eIF-4C that is inhibited by alpha-amanitin and correlated with a transient increase in the relative rate of protein synthesis for eIF-4C. We confirm the transient increase in eIF-4C mRNA abundance by a reverse transcription-PCR-based assay using eIF-4C-specific primers. The first round of DNA replication seems critical for eIF-4C expression, since addition of aphidicolin prior to S phase in the 1-Cell embryo inhibits the magnitude of the increase in eIF-4C expression. Aphidicolin treatment also inhibits the synthesis of an accepted marker for ZGA, the transcription requiring complex (TRC), which is also transiently expressed during the 2-Cell Stage. Incubating late 1-Cell/early 2-Cell embryos in medium containing aphidicolin reveals that the second round of DNA replication is not required for the increase in eIF-4C expression but DNA replication is required for the decrease in both eIF-4C expression and TRC synthesis. The decrease in eIF-4C expression, however, does not require cytokinesis or mitosis, since it occurs when 2-Cell embryos are cultured in the presence of cytochalasin D or nocodazole, respectively. Changes in chromatin structure may be involved in the decrease in both eIF-4C and TRC expression, since neither decrease occurs when 2-Cell embryos are cultured in trapoxin, which is a specific and irreversible inhibitor of histone deacetylase. Results of these experiments suggest that the first round of DNA replication is permissive with respect to ZGA and that the second round is repressive.
Masataka G Suzuki - One of the best experts on this subject based on the ideXlab platform.
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minor zygotic gene activation is essential for mouse preimplantation development
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Kenichiro Abe, Richard M. Schultz, Satoshi Funaya, Dai Tsukioka, Machika Kawamura, Yutaka Suzuki, Masataka G Suzuki, Fugaku AokiAbstract:In mice, transcription initiates at the mid-one-Cell Stage and transcriptional activity dramatically increases during the two-Cell Stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-Cell Stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-Cell Stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.
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Linker histone H1FOO regulates the chromatin structure in mouse zygotes.
FEBS letters, 2018Co-Authors: Satoshi Funaya, Masataka G Suzuki, Masatoshi Ooga, Fugaku AokiAbstract:The chromatin structure in one-Cell-Stage mouse embryos is extremely loose and becomes tighter at the two-Cell Stage. As linker histones are involved in higher-order chromatin structure, we examined the involvement of the linker histone variant H1foo in the change of chromatin looseness between the one- and two-Cell Stages. H1foo knockdown causes the chromatin structure to be tighter in the pronucleus and increases deposition of the histone H3 variant H3.1/3.2 in the peripheral region of the pronucleus in one-Cell-Stage embryos. The decrease in chromatin looseness at the two-Cell Stage is less after overexpressing H1foo. These results suggest that H1foo is involved in the change in chromatin structure via nuclear deposition of H3 variants between the one- and two-Cell Stages.
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regulation of transketolase like 1 gene expression in the murine one Cell Stage embryos
PLOS ONE, 2014Co-Authors: Go Hamamoto, Masataka G Suzuki, Tsukasa Suzuki, Fugaku AokiAbstract:In mice, transcription from the zygotic genome starts at the mid-one-Cell Stage after fertilization. Previous studies showed that an enhancer is not required for transcription at this Stage, and that the enhancer-dependent mechanism of transcription is established during the two-Cell Stage. However, these results were obtained using reporter gene assays with promoters derived from viruses, rather than from endogenous genes. We conducted a reporter-gene assay using the promoter of Tktl1, which is transcribed after fertilization, to investigate the mechanism regulating gene expression at the one-Cell Stage. When a plasmid containing the 2467 bp upstream and 25 bp downstream of the Tktl1 transcription start site (TSS) was microinjected into the nuclei of growing oocytes, and one-Cell Stage and early and late two-Cell-Stage embryos, transcriptional activity was detected in the one-Cell- and two-Cell-Stage embryos, but not in the oocytes. It was highest at the early two-Cell Stage and was reduced at the late two-Cell Stage. The decrease in activity at the late two-Cell Stage was prevented by inhibiting the second round of DNA replication, suggesting that the transcriptionally repressive state is established during the two-Cell Stage by a mechanism coupled to DNA replication. When the Tktl1 promoter was deleted to leave 56 bp upstream of the TSS which includes GC and TATA boxes, transcriptional activity was still detected in one-Cell-Stage embryos, but not early or late two-Cell-Stage embryos. The core promoter of Tktl1 alone seems to be able to induce basal transcription at the one-Cell Stage. These results suggest that repressive chromatin is established after fertilization in two steps, which occur during the transition from the one- to two-Cell Stage and during DNA replication at the two-Cell Stage.
Magdalena Zernickagoetz - One of the best experts on this subject based on the ideXlab platform.
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spatial arrangement of individual 4 Cell Stage blastomeres and the order in which they are generated correlate with blastocyst pattern in the mouse embryo
Mechanisms of Development, 2005Co-Authors: Karolina Piotrowskanitsche, Magdalena ZernickagoetzAbstract:In the unperturbed development of the mouse embryo one of the 2-Cell blastomeres tends to contribute its progeny predominantly to the embryonic and the other to the abembryonic part of the blastocyst. However, a significant minority of embryos (20-30%) do not show this correlation. In this study, we have used non-invasive lineage tracing to determine whether development of blastocyst pattern shows any correlation with the orientation and order of the second cleavage divisions that result in specific positioning of blastomeres at the 4-Cell Stage. Although the orientation and order of the second cleavages are not predetermined, in the great majority (80%) of embryos the spatial arrangement of 4-Cell blastomeres is consistent with one of the second cleavages occurring meridionally and the other equatorially or obliquely with respect to the polar body. In such cleaving embryos, one of the 2-Cell Stage blastomeres tends to contribute to embryonic while the other contributes predominantly to abembryonic part of the blastocyst. Thus, in these embryos the outcome of the first cleavage tends to correlate with the orientation of the blastocyst embryonic-abembryonic axis. However, the order of blastomere divisions predicts a specific polarity for this axis only when the earlier 2-Cell blastomere to divide does so meridionally. In contrast to the above two groups, in those embryos in which both second cleavage divisions occur in a similar orientation, either meridionally or equatorially, we do not observe any tendency for the 2-Cell blastomeres to contribute to specific blastocyst parts. We find that all these groups of embryos develop to term with similar success, with the exception of those in which both second cleavage divisions occur equatorially whose development can be compromised. We conclude that the orientations and order of the second cleavages are not predetermined; they correlate with the development of blastocyst patterning; and that the majority, but not all, of these cleavage patterns allow equally successful development.
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downregulation of par3 and apkc function directs Cells towards the icm in the preimplantation mouse embryo
Journal of Cell Science, 2005Co-Authors: Berenika Plusa, Stephen Frankenberg, Andrew D Chalmers, Annakaterina Hadjantonakis, Catherine A Moore, Nancy Papalopulu, Virginia E Papaioannou, David M Glover, Magdalena ZernickagoetzAbstract:Generation of inside Cells that develop into inner Cell mass (ICM) and outside Cells that develop into trophectoderm is central to the development of the early mouse embryo. Critical to this decision is the development of Cell polarity and the associated asymmetric (differentiative) divisions of the 8-Cell-Stage blastomeres. The underlying molecular mechanisms for these events are not understood. As the Par3/aPKC complex has a role in establishing Cellular polarity and division orientation in other systems, we explored its potential function in the developing mouse embryo. We show that both Par3 and aPKC adopt a polarized localization from the 8-Cell Stage onwards and that manipulating their function re-directs Cell positioning and consequently influences Cell fate. Injection of dsRNA against Par3 or mRNA for a dominant negative form of aPKC into a random blastomere at the 4-Cell Stage directs progeny of the injected Cell into the inside part of the embryo. This appears to result from both an increased frequency by which such Cells undertake differentiative divisions and their decreased probability of retaining outside positions. Thus, the natural spatial allocation of blastomere progeny can be over-ridden by downregulation of Par3 or aPKC, leading to a deceased tendency for them to remain outside and so develop into trophectoderm. In addition, this experimental approach illustrates a powerful means of manipulating gene expression in a specific clonal population of Cells in the preimplantation embryo.
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animal and vegetal poles of the mouse egg predict the polarity of the embryonic axis yet are nonessential for development
Development, 2000Co-Authors: Maria Anna Ciemerych, Daniel Mesnard, Magdalena ZernickagoetzAbstract:Recent studies suggest early (preimplantation) events might be important in the development of polarity in mammalian embryos. We report here lineage tracing experiments with green fluorescent protein showing that Cells located either near to or opposite the polar body at the 8-Cell Stage of the mouse embryo retain their same relative positions in the blastocyst. Thus they come to lie on either end of an axis of symmetry of the blastocyst that has recently been shown to correlate with the anterior-posterior axis of the postimplantation embryo (see R. J. Weber, R. A. Pedersen, F. Wianny, M. J. Evans and M. Zernicka-Goetz (1999). Development 126, 5591–5598). The embryonic axes of the mouse can therefore be related to the position of the polar body at the 8-Cell Stage, and by implication, to the animal-vegetal axis of the zygote. However, we also show that chimeric embryos constructed from 2-Cell Stage blastomeres from which the animal or the vegetal poles have been removed can develop into normal blastocysts and become fertile adult mice. This is also true of chimeras composed of animal or vegetal pole Cells derived through normal cleavage to the 8-Cell Stage. We discuss that although polarity of the postimplantation embryo can be traced back to the 8-Cell Stage and in turn to the organisation of the egg, it is not absolutely fixed by this time.
Michael Wegner - One of the best experts on this subject based on the ideXlab platform.
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sox10 is required for schwann Cell identity and progression beyond the immature schwann Cell Stage
Journal of Cell Biology, 2010Co-Authors: Markus Finzsch, Michael R Bösl, Dies Meijer, Ernst R Tamm, Silke Schreiner, Tatjana I Kichko, Peter W Reeh, Michael WegnerAbstract:Mutations in the transcription factor SOX10 cause neurocristopathies, including Waardenburg-Hirschsprung syndrome and peripheral neuropathies in humans. This is partly attributed to a requirement for Sox10 in early neural crest for survival, maintenance of pluripotency, and specification to several Cell lineages, including peripheral glia. As a consequence, peripheral glia are absent in Sox10-deficient mice. Intriguingly, Sox10 continues to be expressed in these Cells after specification. To analyze glial functions after specification, we specifically deleted Sox10 in immature Schwann Cells by conditional mutagenesis. Mutant mice died from peripheral neuropathy before the seventh postnatal week. Nerve alterations included a thinned perineurial sheath, increased lipid and collagen deposition, and a dramatically altered Cellular composition. Nerve conduction was also grossly aberrant, and neither myelinating nor nonmyelinating Schwann Cells formed. Instead, axons of different sizes remained unsorted in large bundles. Schwann Cells failed to develop beyond the immature Stage and were unable to maintain identity. Thus, our study identifies a novel cause for peripheral neuropathies in patients with SOX10 mutations.