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Current Opinion in Cell Biology Feb 2022The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it... (Review)
Review
The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it possible to study 3D genome organisation in the zygote and early embryo of many different species. Recent studies in human embryos, zebrafish, medaka, and Xenopus have revealed that, similar to previous results in mouse and Drosophila, the zygotic genome is unstructured prior to zygotic genome activation. While these studies show that topologically associating domains are established coincident with zygotic genome activation across species, other 3D genome structures have more varied timing. Here, we review recent studies examining the timing and mechanisms of establishment of 3D genome organisation in the early embryo, and discuss similarities and differences between species. Investigating the establishment of 3D chromatin conformation in early embryos has the potential to reveal novel mechanisms of 3D genome organisation.
Topics: Animals; Chromatin; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Genome; Mice; Zebrafish; Zygote
PubMed: 35065445
DOI: 10.1016/j.ceb.2021.12.004 -
Cell Stem Cell Jun 20222-cell-like cells (2CLCs)-which comprise only ∼1% of murine embryonic stem cells (mESCs)-resemble blastomeres of 2-cell-stage embryos and are used to investigate...
2-cell-like cells (2CLCs)-which comprise only ∼1% of murine embryonic stem cells (mESCs)-resemble blastomeres of 2-cell-stage embryos and are used to investigate zygotic genome activation (ZGA). Here, we discovered that TRIM66 and DAX1 function together as negative regulators of the 2C-like state in mESCs. Chimeric assays confirmed that mESCs lacking TRIM66 or DAX1 function have bidirectional embryonic and extraembryonic differentiation potential. TRIM66 functions by recruiting the co-repressor DAX1 to the Dux promoter, and TRIM66's repressive effect on Dux is dependent on DAX1. A solved crystal structural shows that TRIM66's PHD finger recognizes H3K4-K9me3, and mutational evidence confirmed that TRIM66's PHD finger is essential for its repression of Dux. Thus, beyond expanding the scope of known 2CLC regulators, our study demonstrates that interventions disrupting TRIM66 or DAX1 function in mESCs yield 2CLCs with expanded bidirectional differentiation potential, opening doors for the practical application of these totipotent-like cells.
Topics: Animals; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Genome; Mice; Promoter Regions, Genetic; Zygote
PubMed: 35659877
DOI: 10.1016/j.stem.2022.05.004 -
Clinical and Translational Medicine Dec 2022RNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m C (5-methylcytosine)-coordinating modificatory transcripts are...
BACKGROUND
RNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m C (5-methylcytosine)-coordinating modificatory transcripts are dynamically regulated during oogenesis, and ovarian development is unknown. The purpose of this study was to determine whether NOP2/Sun RNA methyltransferase 5 (Nsun5) deletion leads to suppression of ovarian function and arrest of embryonic development. The regulation of mRNA decay and stability by m C modification is essential at multiple stages during the maternal-to-zygotic (MZT) transition.
METHODS
Mouse ovaries and oocytes with Nsun5 and the KGN cell line were subjected to m C identification, alternative splicing analysis and protein expression. BS-m C-seq, real-time polymerase chain reaction, Western blot, immunofluorescence and actinomycin D treatment assays were used. In particular, BS-m C-seq revealed a dynamic pattern of m C sites and genes in the ovaries between Nsun5 and WT mice at the 2-month and 6-month stages. Diverse bioinformatic tools were employed to identify target genes for Nsun5.
RESULTS
Here, a maternal mRNA stability study showed that deletion of the m C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m C revealed that the level of m C decreased in a time-dependent manner after Nsun5 knockout. Regarding the molecular mechanism, we found that Nsun5 deficiency caused a m C decline in the exon and 3'UTR regions that influenced the translation efficiency of Mitotic arrest deficient 2 like 2 (MAD2L2) and Growth differentiation factor 9 (GDF9) in the ovary. Mechanistic investigation of alternative splicing indicated that Nsun5 triggers aberrant events in the exon region of Brd8.
CONCLUSIONS
Nsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m C-regulated maternal mRNA stabilization is essential for MZT transition.
Topics: Pregnancy; Female; Mice; Animals; RNA, Messenger, Stored; Methyltransferases; RNA; Zygote; RNA Stability
PubMed: 36495115
DOI: 10.1002/ctm2.1137 -
Current Topics in Developmental Biology 2021The fertilized frog egg contains all the materials needed to initiate development of a new organism, including stored RNAs and proteins deposited during oogenesis, thus... (Review)
Review
The fertilized frog egg contains all the materials needed to initiate development of a new organism, including stored RNAs and proteins deposited during oogenesis, thus the earliest stages of development do not require transcription. The onset of transcription from the zygotic genome marks the first genetic switch activating the gene regulatory network that programs embryonic development. Zygotic genome activation occurs after an initial phase of transcriptional quiescence that continues until the midblastula stage, a period called the midblastula transition, which was first identified in Xenopus. Activation of transcription is programmed by maternally supplied factors and is regulated at multiple levels. A similar switch exists in most animals and is of great interest both to developmental biologists and to those interested in understanding nuclear reprogramming. Here we review in detail our knowledge on this major switch in transcription in Xenopus and place recent discoveries in the context of a decades old problem.
Topics: Animals; Genome; Oogenesis; Xenopus laevis; Zygote
PubMed: 34074529
DOI: 10.1016/bs.ctdb.2021.03.003 -
Current Opinion in Cell Biology Apr 2022The actin and microtubule cytoskeletons of mammalian oocytes and zygotes exist in distinct forms at various subcellular locations. This enables each cytoskeletal system... (Review)
Review
The actin and microtubule cytoskeletons of mammalian oocytes and zygotes exist in distinct forms at various subcellular locations. This enables each cytoskeletal system to perform vastly different functions in time and space within the same cell. In recent years, key discovery enabling tools including light-sensitive microscopy assays have helped to illuminate cytoskeletal form and function in female reproductive cell biology. New findings include unexpected participation of F-actin in oocyte chromosome segregation, oocyte specific modes of spindle self-organization as well as existence of nuclear actin polymers whose functions are only starting to emerge. Functional actin-microtubule interactions have also been identified as an important feature that supports mammalian embryo development. Other advances have revealed reproductive age-related changes in chromosome structure and dynamics that predispose mammalian eggs to aneuploidy.
Topics: Actins; Animals; Female; Mammals; Meiosis; Oocytes; Spindle Apparatus; Zygote
PubMed: 35364486
DOI: 10.1016/j.ceb.2022.02.007 -
Journal of Computational Biology : a... Sep 2020We build a theoretical model of morphogenesis. This model describes cell fate in the developing organism using the notion of epigenetic code of each cell. Namely, given...
We build a theoretical model of morphogenesis. This model describes cell fate in the developing organism using the notion of epigenetic code of each cell. Namely, given the epigenetic spectra of a cell and its neighboring cells, we can determine the corresponding cell event it will perform. This means that the properties of a group of cells (comprising an embryo or its part) at any time point are also known, and thus, the evolution of an embryo can be described. By this strategy, it is possible to establish the tissue, organ, or embryo shapes at any time, starting from a zygote. As an essential part of the model, the formalization of the notion of cell potency is introduced, and the related properties are discussed.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Embryonic Development; Epigenesis, Genetic; Humans; Models, Theoretical; Morphogenesis; Zygote
PubMed: 32031875
DOI: 10.1089/cmb.2019.0414 -
Cells Sep 2021Recently, it was pointed out that classic models for the evolution of anisogamy do not take into account the possibility of parthenogenetic reproduction, even though sex...
Recently, it was pointed out that classic models for the evolution of anisogamy do not take into account the possibility of parthenogenetic reproduction, even though sex is facultative in many relevant taxa (e.g., algae) that harbour both anisogamous and isogamous species. Here, we complement this recent analysis with an approach where we assume that the relationship between progeny size and its survival may differ between parthenogenetically and sexually produced progeny, favouring either the former or the latter. We show that previous findings that parthenogenesis can stabilise isogamy relative to the obligate sex case, extend to our scenarios. We additionally investigate two different ways for one mating type to take over the entire population. First, parthenogenesis can lead to biased sex ratios that are sufficiently extreme that one type can displace the other, leading to de facto asexuality for the remaining type that now lacks partners to fuse with. This process involves positive feedback: microgametes, being numerous, lack opportunities for syngamy, and should they proliferate parthenogenetically, the next generation makes this asexual route even more prominent for microgametes. Second, we consider mutations to strict asexuality in producers of micro- or macrogametes, and show that the prospects of asexual invasion depend strongly on the mating type in which the mutation arises. Perhaps most interestingly, we also find scenarios in which parthenogens have an intrinsic survival advantage yet facultatively sexual isogamous populations are robust to the invasion of asexuals, despite us assuming no genetic benefits of recombination. Here, equal contribution from both mating types to zygotes that are sufficiently well provisioned can outweigh the additional costs associated with syngamy.
Topics: Biological Evolution; Gametogenesis; Germ Cells; Models, Biological; Mutation; Parthenogenesis; Phaeophyceae; Zygote
PubMed: 34572116
DOI: 10.3390/cells10092467 -
Die Naturwissenschaften Jul 2020The egg stages of animal life cycles are underappreciated in terms of their capacity for dispersal, protection, and biotic and abiotic interactions. Some of the most... (Review)
Review
The egg stages of animal life cycles are underappreciated in terms of their capacity for dispersal, protection, and biotic and abiotic interactions. Some of the most intriguing egg morphologies are seen in stick and leaf insects (Phasmatodea). Phasmids are charismatic insects, particularly due to their incredible camouflage, though a lesser-known fact is that their eggs are incredibly diverse in shape and structure, reflecting varying ecological niches. Perhaps most remarkable are those eggs which appear to resemble plant seeds in both their appearance and means of dispersal, such as via water and animal vectors. Numerous hypotheses surrounding the function of these egg morphologies and their apparent convergence with seeds have been proposed; however, empirical evidence remains lacking. Here, we present an initial synthesis of available evidence surrounding the ecology and dispersal strategies of phasmid eggs and weigh up the evidence for convergent evolution between phasmid eggs and seeds. In doing so, we highlight areas where further research is needed and discuss how the ecology of phasmid eggs may interplay with other aspects of phasmid ecology, distribution, and evolution.
Topics: Animal Distribution; Animals; Biological Evolution; Neoptera; Plants; Seeds; Zygote
PubMed: 32737596
DOI: 10.1007/s00114-020-01690-1 -
DNA Repair Sep 2022Mammalian zygotes are hypersensitive to radiation exposure compared with later-stage embryos and somatic cells, which may be due to an unusual DNA damage response (DDR)....
Mammalian zygotes are hypersensitive to radiation exposure compared with later-stage embryos and somatic cells, which may be due to an unusual DNA damage response (DDR). DNA damage checkpoints are an essential part of the DDR, allowing for faithful replication of cells. Although the DDR and radiosensitivity of somatic cells are dependent on the cell cycle phase, it remains largely unclear how the irradiation of zygotes at different phases affects cell cycle progression and preimplantation development. Here, mouse zygotes were irradiated with 10 Gy γ-rays at all four cell cycle phases. DNA damage checkpoints were activated by γ-irradiation at the G2 phase, but not at the G1, S, and M phases. The absence of DNA damage checkpoints at the G1 and M phases seems to be due to the low abundance of phosphorylated CHK2, which plays a key role in checkpoint activation in response to ionizing radiation. The cause of the inoperative S phase checkpoint may lie downstream of CHK2 activation. The inactive DNA damage checkpoints at the G1 and S phases contributed to micronucleus formation in the subsequent 2-cell stage, whereas irradiation at the M phase led to the highest incidence of chromatin bridges. The low developmental rates of embryos irradiated at the G1, S, and M phases suggest that embryos with these two types of chromatin abnormalities are prone to developmental failure. Taken together, these results suggest that the radiosensitivity of zygotes can be ascribed to a defective DDR at the G1, S, and M phases.
Topics: Animals; Cell Cycle; Cell Division; Chromatin; DNA Damage; Mammals; Mice; Radiation Tolerance; Zygote
PubMed: 35863142
DOI: 10.1016/j.dnarep.2022.103370 -
Food and Chemical Toxicology : An... May 2023Acrylamide (ACR) is an important chemical raw material for wastewater treatment, paper industry and textile industry, which is widely exposed from occupational,...
Acrylamide (ACR) is an important chemical raw material for wastewater treatment, paper industry and textile industry, which is widely exposed from occupational, environmental and dietary situation. ACR has neurotoxicity, genotoxicity, potential carcinogenicity and reproductive toxicity. Recent study indicates that ACR affected oocyte maturation quality. In the present study, we reported the effects of ACR exposure on zygotic genome activation (ZGA) in embryos and its related mechanism. Our results showed that ACR treatment caused 2-cell arrest in mouse embryos, indicating the failure of ZGA, which was confirmed by decreased global transcription levels and aberrant expression of ZGA-related and maternal factors. We found that histone modifications such as H3K9me3, H3K27me3 and H3K27ac levels were altered, and this might be due to the occurrence of DNA damage, showing with positive γ-H2A.X signal. Moreover, mitochondrial dysfunction and high levels of ROS were detected in ACR treated embryos, indicating that ACR induced oxidative stress, and this might further cause abnormal distribution of endoplasmic reticulum, Golgi apparatus and lysosomes. In conclusion, our results indicated that ACR exposure disrupted ZGA by inducing mitochondria-based oxidative stress, which further caused DNA damage, aberrant histone modifications and organelles in mouse embryos.
Topics: Mice; Animals; Acrylamide; Zygote; Oxidative Stress; Protein Processing, Post-Translational; DNA Damage
PubMed: 36997053
DOI: 10.1016/j.fct.2023.113753