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Cell Reports Feb 2023The maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation...
The maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation of maternal transcripts. We employed metabolic mRNA sequencing (SLAMseq) to deconvolute the compound embryonic transcriptome in zebrafish. While mitochondrial zygotic transcripts prevail prior to MZT, we uncover the spurious transcription of hundreds of short and intron-poor genes as early as the 2-cell stage. Upon ZGA, most zygotic transcripts originate from thousands of maternal-zygotic (MZ) genes that are transcribed at rates comparable to those of hundreds of purely zygotic genes and replenish maternal mRNAs at distinct timescales. Rapid replacement of MZ transcripts involves transcript decay features unrelated to major maternal degradation pathways and promotes de novo synthesis of the core gene expression machinery by increasing poly(A)-tail length and translation efficiency. SLAMseq hence provides insights into the timescales, molecular features, and regulation of MZT during zebrafish embryogenesis.
Topics: Animals; Zebrafish; Embryonic Development; Zygote; RNA, Messenger; Transcriptome; Gene Expression Regulation, Developmental
PubMed: 36757845
DOI: 10.1016/j.celrep.2023.112070 -
International Journal of Molecular... Jan 2024Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a... (Review)
Review
Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.
Topics: Animals; Pregnancy; Female; Male; Zygote; Histone Code; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Semen; Embryonic Development; Mammals
PubMed: 38338738
DOI: 10.3390/ijms25031459 -
The Journal of Reproduction and... Aug 2017After fertilization, the genomes derived from an oocyte and spermatozoon are in a transcriptionally silent state before becoming activated at a species-specific time. In... (Review)
Review
After fertilization, the genomes derived from an oocyte and spermatozoon are in a transcriptionally silent state before becoming activated at a species-specific time. In mice, the initiation of transcription occurs at the mid-one-cell stage, which represents the start of the gene expression program. A recent RNA sequencing analysis revealed that the gene expression pattern of one-cell embryos is unique and changes dramatically at the two-cell stage. However, the mechanism regulating this alteration has not yet been elucidated. It has been shown that chromatin structure and epigenetic factors change dynamically between the one- and two-cell stages. In this article, we review the characteristics of transcription, chromatin structure, and epigenetic factors in one- and two-cell mouse embryos and discuss the involvement of chromatin structure and epigenetic factors in the alteration of transcription that occurs between these stages.
Topics: Animals; Chromatin; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Transcriptional Activation; Zygote
PubMed: 28579579
DOI: 10.1262/jrd.2017-058 -
Open Biology Dec 2018The onset of metazoan development requires that two terminally differentiated germ cells, a sperm and an oocyte, become reprogrammed to the totipotent embryo, which can... (Review)
Review
The onset of metazoan development requires that two terminally differentiated germ cells, a sperm and an oocyte, become reprogrammed to the totipotent embryo, which can subsequently give rise to all the cell types of the adult organism. In nearly all animals, maternal gene products regulate the initial events of embryogenesis while the zygotic genome remains transcriptionally silent. Developmental control is then passed from mother to zygote through a process known as the maternal-to-zygotic transition (MZT). The MZT comprises an intimately connected set of molecular events that mediate degradation of maternally deposited mRNAs and transcriptional activation of the zygotic genome. This essential developmental transition is conserved among metazoans but is perhaps best understood in the fruit fly, Drosophila melanogaster. In this article, we will review our understanding of the events that drive the MZT in Drosophila embryos and highlight parallel mechanisms driving this transition in other animals.
Topics: Animals; Drosophila melanogaster; Embryonic Development; Female; Gene Expression Regulation, Developmental; Male; RNA Stability; RNA, Messenger, Stored; Transcription, Genetic; Transcriptional Activation; Zygote
PubMed: 30977698
DOI: 10.1098/rsob.180183 -
The International Journal of... 2019Early embryonic development is characterized by a plethora of very complex and simultaneously operating processes, which are constantly changing cellular morphology and... (Review)
Review
Early embryonic development is characterized by a plethora of very complex and simultaneously operating processes, which are constantly changing cellular morphology and behaviour. After fertilization, blastomeres of the newly created embryo undergo global epigenetic changes and simultaneously initiate transcription from the zygotic genome and differentiation forming separate cell lineages. Some of these mechanisms were extensively studied during the last several decades and valuable insight was gained into how these processes are regulated at the molecular level. We have, however, a still very limited understanding of how multiple events are coordinated during rapid development of an early mammalian embryo. In this review, we discuss some aspects of early embryonic development in mammals, namely the fidelity of chromosome segregation and occurrence of aneuploidy, as well as the clinical applications of cell cycle monitoring in human embryos.
Topics: Aneuploidy; Animals; Blastomeres; Cell Cycle; Chromosome Segregation; Embryo, Mammalian; Embryonic Development; Female; Humans; Pregnancy; Spindle Apparatus; Zygote
PubMed: 30785212
DOI: 10.1387/ijdb.180400ma -
Reproduction (Cambridge, England) May 2021Elucidating the mechanisms underpinning fertilisation is essential to optimising IVF procedures. One of the critical steps involves paternal chromatin reprogramming, in...
Elucidating the mechanisms underpinning fertilisation is essential to optimising IVF procedures. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. HIRA is the main H3.3 chaperone governing this protamine-to-histone exchange. Failure of this step results in abnormally fertilised zygotes containing only one pronucleus (1PN), in contrast to normal two-pronuclei (2PN) zygotes. 1PN zygotes are frequently observed in IVF treatments, but the genotype-phenotype correlation remains elusive. We investigated the maternal functions of two other molecules of the HIRA complex, Cabin1 and Ubn1, in mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed an abnormal 1PN zygote phenotype. We then studied human 1PN zygotes and found that the HIRA complex was absent in 1PN zygotes that lacked the male pronucleus. This shows that the role of the HIRA complex in male pronucleus formation potentially has coherence from mice to humans. Furthermore, rescue experiments in mouse showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of HIRA. We have demonstrated that HIRA complex regulates male pronucleus formation in mice and is implicated in humans, that both CABIN1 and UBN1 components of the HIRA complex are equally essential for male pronucleus formation, and that rescue is feasible.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Cycle Proteins; Cell Nucleus; Chromatin Assembly and Disassembly; Female; Fertilization in Vitro; Histone Chaperones; Histones; Humans; Male; Mice; Mice, Inbred C57BL; Nuclear Proteins; Phenotype; Transcription Factors; Zygote
PubMed: 33835048
DOI: 10.1530/REP-20-0636 -
The Journal of Reproduction and... Dec 2009The supply of human oocytes is very limited. This restricts not only certain assisted reproduction procedures in IVF clinics where recipients wait for oocytes from... (Review)
Review
The supply of human oocytes is very limited. This restricts not only certain assisted reproduction procedures in IVF clinics where recipients wait for oocytes from donors, but also development of some promising approaches, like therapeutic nuclear transfer with subsequent derivation of patient compatible embryonic stem cells. Moreover, in some patients, collected oocytes exhibit certain specific defects, and logically, we can expect that after fertilization, the embryos arising from these defective oocytes may not develop or that their development might eventually be compromised. For this reason, an increased effort to determine how to repair oocytes is evident in the literature. In general, abnormalities (defects) can be detected in different oocyte components, the zona pellucida, cytoplasm, nucleus (chromosomes) and nucleolus. Whereas defects of a nuclear component are impossible (nuclear DNA) or very hard to repair (nucleolus), zona pellucida abnormalities and cytoplasm defects (for example, if containing mutated mitochondrial DNA, mtDNA) can be repaired in some cases with the help of micromanipulation schemes. In the present article, we will briefly outline the current methodological approaches that can be used to repair the oocyte or one-cell stage embryo.
Topics: Animals; Female; Humans; Infertility; Male; Micromanipulation; Oocytes; Reproductive Techniques, Assisted; Zygote
PubMed: 20075602
DOI: 10.1262/jrd.09-085h -
Cell Proliferation Mar 2023Pre-replication complex (pre-RC) is critical for DNA replication initiation. CDT1 and MCM2 are the subunits of pre-RC, and proper regulation of CDT1 and MCM2 are...
Pre-replication complex (pre-RC) is critical for DNA replication initiation. CDT1 and MCM2 are the subunits of pre-RC, and proper regulation of CDT1 and MCM2 are necessary for DNA replication and cell proliferation. The present study aimed to explore the role of CDT1 and MCM2 in oocyte meiotic maturation and early embryonic development. The depletion and overexpression of Cdt1 and Mcm2 in oocyte and zygote were achieved by microinjecting specific siRNA and mRNA to explored their functions in oocyte meiotic maturation and embryonic development. Then, we examined the effect of CDT1 and MCM2 on other signal pathways by immunostaining the expression of related maker genes. We showed that neither depletion nor overexpression of Cdt1 affected oocyte meiotic progressions. The CDT1 was degraded in S phase and remained at a low level in G2 phase of zygote. Exogenous expression of Cdt1 in G2 phase led to embryo attest at zygote stage. Mechanistically, CDT1 overexpression induced DNA re-replication and thus DNA damage check-point activation. Protein abundance of MCM2 was stable throughout the cell cycle, and embryos with overexpressed MCM2 could develop to blastocysts normally. Overexpression or depletion of Mcm2 also had no effect on oocyte meiotic maturation. Our results indicate that pre-RC subunits CDT1 and MCM2 are not involved in oocyte meiotic maturation. In zygote, CDT1 but not MCM2 is the major regulator of DNA replication in a cell cycle dependent manner. Furthermore, its' degradation is essential for zygotes to prevent from DNA re-replication in G2 stage.
Topics: Zygote; Cell Cycle Proteins; DNA Replication; Cell Cycle; DNA
PubMed: 36479743
DOI: 10.1111/cpr.13377 -
Current Topics in Developmental Biology 2015In Xenopus, the germline is specified by the inheritance of germ-plasm components synthesized at the beginning of oogenesis. Only the cells in the early embryo that... (Review)
Review
In Xenopus, the germline is specified by the inheritance of germ-plasm components synthesized at the beginning of oogenesis. Only the cells in the early embryo that receive germ plasm, the primordial germ cells (PGCs), are competent to give rise to the gametes. Thus, germ-plasm components continue the totipotent potential exhibited by the oocyte into the developing embryo at a time when most cells are preprogrammed for somatic differentiation as dictated by localized maternal determinants. When zygotic transcription begins at the mid-blastula transition, the maternally set program for somatic differentiation is realized. At this time, genetic control is ceded to the zygotic genome, and developmental potential gradually becomes more restricted within the primary germ layers. PGCs are a notable exception to this paradigm and remain transcriptionally silent until the late gastrula. How the germ-cell lineage retains full potential while somatic cells become fate restricted is a tale of translational repression, selective degradation of somatic maternal determinants, and delayed activation of zygotic transcription.
Topics: Animals; Cell Lineage; Cytoskeleton; Female; Germ Cells; RNA Stability; Xenopus; Zygote
PubMed: 26358876
DOI: 10.1016/bs.ctdb.2015.07.021 -
Plant Physiology Jan 2017A comparison of eudicot and monocot model plants explores recent advances and open questions on gene regulatory networks during zygote development, parental influences... (Review)
Review
A comparison of eudicot and monocot model plants explores recent advances and open questions on gene regulatory networks during zygote development, parental influences on early embryogenesis, zygotic genome activation, and cell fate determination.
Topics: Cell Communication; Cell Differentiation; Cell Division; Cell Lineage; Gene Regulatory Networks; Genome, Plant; Genomic Imprinting; Indoleacetic Acids; Magnoliopsida; Plant Growth Regulators; Zygote
PubMed: 27909044
DOI: 10.1104/pp.16.01406