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Nature Communications Jun 2023Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been...
Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.
Topics: Animals; Mice; Embryonic Development; Gene Expression Regulation, Developmental; Retroelements; Solubility; Transcription Factors; Zygote
PubMed: 37339952
DOI: 10.1038/s41467-023-39344-1 -
Philosophical Transactions of the Royal... Oct 2020Cell polarity is the asymmetric distribution of cellular components along a defined axis. Polarity relies on complex signalling networks between conserved patterning... (Review)
Review
Cell polarity is the asymmetric distribution of cellular components along a defined axis. Polarity relies on complex signalling networks between conserved patterning proteins, including the PAR (titioning defective) proteins, which become segregated in response to upstream symmetry breaking cues. Although the mechanisms that drive the asymmetric localization of these proteins are dependent upon cell type and context, in many cases the regulation of actomyosin cytoskeleton dynamics is central to the transport, recruitment and/or stabilization of these polarity effectors into defined subcellular domains. The transport or advection of PAR proteins by an actomyosin flow was first observed in the s zygote more than a decade ago. Since then a multifaceted approach, using molecular methods, high-throughput screens, and biophysical and computational models, has revealed further aspects of this flow and how polarity regulators respond to and modulate it. Here, we review recent findings on the interplay between actomyosin flow and the PAR patterning networks in the polarization of the zygote. We also discuss how these discoveries and developed methods are shaping our understanding of other flow-dependent polarizing systems. This article is part of a discussion meeting issue 'Contemporary morphogenesis'.
Topics: Actomyosin; Animals; Body Patterning; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Polarity; Embryo, Nonmammalian; Protein Serine-Threonine Kinases; Signal Transduction; Zygote
PubMed: 32829680
DOI: 10.1098/rstb.2019.0555 -
Cytoskeleton (Hoboken, N.J.) Dec 2022Centrosomes serve as a site for microtubule nucleation and these microtubules will grow and interact with the motor protein dynein at the cortex. The position of the...
Centrosomes serve as a site for microtubule nucleation and these microtubules will grow and interact with the motor protein dynein at the cortex. The position of the centrosomes determines where the mitotic spindle will develop across all cell types. Centrosome positioning is achieved through dynein and microtubule-mediated force generation. The mechanism and regulation of force generation during centrosome positioning are not fully understood. Centrosome and pronuclear movement in the first cell cycle of the Caenorhabditis elegans early embryo undergoes both centration and rotation prior to cell division. The proteins LET-99 and GPB-1 have been postulated to have a role in force generation associated with pronuclear centration and rotation dynamics. When the expression of these proteins is perturbed, pronuclear positioning exhibits a movement defect characterized by oscillatory ("wobble") behavior of the pronuclear complex (PNC). To determine if this movement defect is due to an effect on cortical dynein distribution, we utilize RNAi-mediated knockdown of LET-99 and GPB-1 to induce wobble and assay for any effects on GFP-tagged dynein localization in the early C. elegans embryo. To compare and quantify the movement defect produced by the knockdown of LET-99 and GPB-1, we devised a quantification method that measures the strength of wobble ("wobble metric") observed under these experimental conditions. Our quantification of pronuclear complex dynamics and dynein localization shows that loss of LET-99 and GPB-1 induces a similar movement defect which is independent of cortical dynein localization in the early C. elegans embryo.
Topics: Animals; Caenorhabditis elegans; Dyneins; Caenorhabditis elegans Proteins; Zygote; Spindle Apparatus; Microtubules; Centrosome
PubMed: 36214774
DOI: 10.1002/cm.21733 -
Genomics, Proteomics & Bioinformatics Oct 2023During mammalian preimplantation development, a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination, ultimately forming a mature... (Review)
Review
During mammalian preimplantation development, a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination, ultimately forming a mature blastocyst. Along with compaction, the establishment of apicobasal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate choice. Although the lineage segregation of the inner cell mass (ICM) and trophectoderm (TE) is the first symbol of cell differentiation, several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages, including the 2- and 4-cell stages. The underlying mechanisms of early cell fate determination have long been an important research topic. In this review, we summarize the molecular events that occur during early embryogenesis, as well as the current understanding of their regulatory roles in cell fate decisions. Moreover, as powerful tools for early embryogenesis research, single-cell omics techniques have been applied to both mouse and human preimplantation embryos and have contributed to the discovery of cell fate regulators. Here, we summarize their applications in the research of preimplantation embryos, and provide new insights and perspectives on cell fate regulation.
Topics: Humans; Animals; Mice; Cell Differentiation; Embryo, Mammalian; Blastocyst; Embryonic Development; Zygote; Cell Lineage; Gene Expression Regulation, Developmental; Mammals
PubMed: 37075831
DOI: 10.1016/j.gpb.2023.03.001 -
The Plant Cell Mar 2021After double fertilization, zygotic embryogenesis initiates a new life cycle, and stem cell homeostasis in the shoot apical meristem (SAM) and root apical meristem (RAM)...
After double fertilization, zygotic embryogenesis initiates a new life cycle, and stem cell homeostasis in the shoot apical meristem (SAM) and root apical meristem (RAM) allows plants to produce new tissues and organs continuously. Here, we report that mutations in DEAD-BOX RNA HELICASE 27 (RH27) affect zygote division and stem cell homeostasis in Arabidopsis (Arabidopsis thaliana). The strong mutant allele rh27-1 caused a zygote-lethal phenotype, while the weak mutant allele rh27-2 led to minor defects in embryogenesis and severely compromised stem cell homeostasis in the SAM and RAM. RH27 is expressed in embryos from the zygote stage, and in both the SAM and RAM, and RH27 is a nucleus-localized protein. The expression levels of genes related to stem cell homeostasis were elevated in rh27-2 plants, alongside down-regulation of their regulatory microRNAs (miRNAs). Further analyses of rh27-2 plants revealed reduced levels of a large subset of miRNAs and their pri-miRNAs in shoot apices and root tips. In addition, biochemical studies showed that RH27 associates with pri-miRNAs and interacts with miRNA-biogenesis components, including DAWDLE, HYPONASTIC LEAVES 1, and SERRATE. Therefore, we propose that RH27 is a component of the microprocessor complex and is critical for zygote division and stem cell homeostasis.
Topics: Arabidopsis; Arabidopsis Proteins; Cell Nucleus; Embryonic Development; Gene Expression Regulation, Plant; MicroRNAs; Zygote
PubMed: 33751089
DOI: 10.1093/plcell/koaa001 -
Genome Biology Apr 2024Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However,...
BACKGROUND
Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However, the timing and functional significance of the remodeling during plant gametogenesis remain obscure.
RESULTS
Here we show that DNA methylation remodeling starts after male meiosis in rice, with non-CG methylation, particularly at CHG sites, being first enhanced in the microspore and subsequently decreased in sperm. Functional analysis of rice CHG methyltransferase genes CMT3a and CMT3b indicates that CMT3a functions as the major CHG methyltransferase in rice meiocyte, while CMT3b is responsible for the increase of CHG methylation in microspore. The function of the two histone demethylases JMJ706 and JMJ707 that remove H3K9me2 may contribute to the decreased CHG methylation in sperm. During male gametogenesis CMT3a mainly silences TE and TE-related genes while CMT3b is required for repression of genes encoding factors involved in transcriptional and translational activities. In addition, CMT3b functions to repress zygotic gene expression in egg and participates in establishing the zygotic epigenome upon fertilization.
CONCLUSION
Collectively, the results indicate that DNA methylation is dynamically remodeled during male gametogenesis, distinguish the function of CMT3a and CMT3b in sex cells, and underpin the functional significance of DNA methylation remodeling during rice reproduction.
Topics: DNA Methylation; Oryza; Seeds; Methyltransferases; Gametogenesis; Gene Expression Regulation, Plant
PubMed: 38566207
DOI: 10.1186/s13059-024-03222-w -
Developmental Dynamics : An Official... Feb 2022Divergent morphology and placentation of Poeciliids make them suitable model for investigating how evolutionary selection has altered and conserved the developmental...
BACKGROUND
Divergent morphology and placentation of Poeciliids make them suitable model for investigating how evolutionary selection has altered and conserved the developmental mechanisms. However, there is limited description of their embryonic staging, despite representing a key evolutionary node that shares developmental strategy with placental vertebrates. Here, we describe the embryonic developmental stages of Gambusia holbrooki from zygote to parturition using freshly harvested embryos.
RESULTS
We defined 40 embryonic stages using a numbered (stages 0-39; zygote to parturition, respectively) and named (grouped into seven periods, ie, zygote, cleavage, blastula, gastrula, segmentation, pharyngula, and parturition) staging system. Two sets of quantitative (ie, egg diameter, embryonic total length, otic vesicle closure index, heart rates, the number of caudal fin rays and elements) and qualitative (ie, three-dimensional analysis of images and key morphological criteria) data were acquired and used in combination to describe each stage. All 40 stages are separated by well-defined morphological traits, revealing developmental novelties that are influenced by narrow perivitelline space, placentation, internal gestation, and sex differentiation.
CONCLUSIONS
The principal diagnostic features described are quick, reliable, and easy to apply. This system will benefit researchers investigating molecular ontogeny, particularly sexual differentiation mechanisms in G. holbrooki.
Topics: Animals; Blastula; Cyprinodontiformes; Embryonic Development; Female; Placenta; Pregnancy; Zygote
PubMed: 34139034
DOI: 10.1002/dvdy.388 -
Cellular and Molecular Life Sciences :... May 2020Maternal RNAs and proteins in the oocyte contribute to early embryonic development. After fertilization, these maternal factors are cleared and embryonic development is... (Review)
Review
Maternal RNAs and proteins in the oocyte contribute to early embryonic development. After fertilization, these maternal factors are cleared and embryonic development is determined by an individual's own RNAs and proteins, in a process called the maternal-to-zygotic transition. Zygotic transcription is initially inactive, but is eventually activated by maternal transcription factors. The timing and molecular mechanisms involved in zygotic genome activation (ZGA) have been well-described in many species. Among birds, a transcriptome-based understanding of ZGA has only been explored in chickens by RNA sequencing of intrauterine embryos. RNA sequencing of chicken intrauterine embryos, including oocytes, zygotes, and Eyal-Giladi and Kochav (EGK) stages I-X has enabled the identification of differentially expressed genes between consecutive stages. These studies have revealed that there are two waves of ZGA: a minor wave at the one-cell stage (shortly after fertilization) and a major wave between EGK.III and EGK.VI (during cellularization). In the chicken, the maternal genome is activated during minor ZGA and the paternal genome is quiescent until major ZGA to avoid transcription from supernumerary sperm nuclei. In this review, we provide a detailed overview of events in intrauterine embryonic development in birds (and particularly in chickens), as well as a transcriptome-based analysis of ZGA.
Topics: Animals; Chick Embryo; Chickens; Embryonic Development; Gene Expression Regulation, Developmental; Genome; Oocytes; RNA, Messenger, Stored; Transcriptome; Zygote
PubMed: 31728579
DOI: 10.1007/s00018-019-03360-6 -
The Potential Role of Schistosome-Associated Factors as Therapeutic Modulators of the Immune System.Infection and Immunity Jul 2020The parasites and eggs of helminths, including schistosomes, are associated with factors that can modulate the nature and outcomes of host immune responses, particularly... (Review)
Review
The parasites and eggs of helminths, including schistosomes, are associated with factors that can modulate the nature and outcomes of host immune responses, particularly enhancing type 2 immunity and impairing the effects of type 1 and type 17 immunity. The main species of schistosomes that cause infection in humans are capable of generating a microenvironment that allows survival of the parasite by evasion of the immune response. Schistosome infections are associated with beneficial effects on chronic immune disorders, including allergies, autoimmune diseases, and alloimmune responses. Recently, there has been increasing research interest in the role of schistosomes in immunoregulation during human infection, and the mechanisms underlying these roles continue to be investigated. Further studies may identify potential opportunities to develop new treatments for immune disease. In this review, we provide an update on the advances in our understanding of schistosome-associated modulation of the cells of the innate and adaptive immune systems as well as the potential role of schistosome-associated factors as therapeutic modulators of immune disorders, including allergies, autoimmune diseases, and transplant immunopathology. We also discuss potential opportunities for targeting schistosome-induced immunoregulation for future translation to the clinical setting.
Topics: Adaptive Immunity; Animals; Autoimmune Diseases; Hypersensitivity; Immune Evasion; Immunity, Innate; Immunologic Factors; Immunomodulation; Immunotherapy; Organ Transplantation; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Th1 Cells; Th17 Cells; Th2 Cells; Zygote
PubMed: 32341115
DOI: 10.1128/IAI.00754-19 -
Open Biology Jun 2022POUV is a relatively newly emerged class of POU transcription factors present in jawed vertebrates (Gnathostomata). The function of POUV-class proteins is inextricably... (Review)
Review
POUV is a relatively newly emerged class of POU transcription factors present in jawed vertebrates (Gnathostomata). The function of POUV-class proteins is inextricably linked to zygotic genome activation (ZGA). A large body of evidence now extends the role of these proteins to subsequent developmental stages. While some functions resemble those of other POU-class proteins and are related to neuroectoderm development, others have emerged . The most notable of the latter functions is pluripotency control by Oct4 in mammals. In this review, we focus on these functions in the best-studied species harbouring POUV proteins-zebrafish, (anamniotes) and mammals (amniotes). Despite the broad diversity of their biological functions in vertebrates, POUV proteins exert a common feature related to their role in safeguarding the undifferentiated state of cells. Here we summarize numerous pieces of evidence for these specific functions of the POUV-class proteins and recap available loss-of-function data.
Topics: Animals; Gene Expression Regulation, Developmental; Mammals; Xenopus laevis; Zebrafish; Zebrafish Proteins; Zygote
PubMed: 35765816
DOI: 10.1098/rsob.220065