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Nature Communications Feb 2021A new life begins with the unification of the maternal and paternal chromosomes upon fertilization. The parental chromosomes first become enclosed in two separate...
A new life begins with the unification of the maternal and paternal chromosomes upon fertilization. The parental chromosomes first become enclosed in two separate pronuclei near the surface of the fertilized egg. The mechanisms that then move the pronuclei inwards for their unification are only poorly understood in mammals. Here, we report two mechanisms that act in concert to unite the parental genomes in fertilized mouse eggs. The male pronucleus assembles within the fertilization cone and is rapidly moved inwards by the flattening cone. Rab11a recruits the actin nucleation factors Spire and Formin-2 into the fertilization cone, where they locally nucleate actin and further accelerate the pronucleus inwards. In parallel, a dynamic network of microtubules assembles that slowly moves the male and female pronuclei towards the cell centre in a dynein-dependent manner. Both mechanisms are partially redundant and act in concert to unite the parental pronuclei in the zygote's centre.
Topics: Actins; Animals; Cell Nucleus; Female; Fertilization; Formins; Gene Expression Regulation, Developmental; Genes, Reporter; Green Fluorescent Proteins; Luminescent Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Microfilament Proteins; Microtubules; Movement; Nerve Tissue Proteins; Oocytes; Spermatozoa; Zygote; rab GTP-Binding Proteins; Red Fluorescent Protein
PubMed: 33547291
DOI: 10.1038/s41467-021-21020-x -
Current Topics in Developmental Biology 2020Drosophila melanogaster embryos develop initially as a syncytium of totipotent nuclei and subsequently, once cellularized, undergo morphogenetic movements associated... (Review)
Review
Drosophila melanogaster embryos develop initially as a syncytium of totipotent nuclei and subsequently, once cellularized, undergo morphogenetic movements associated with gastrulation to generate the three somatic germ layers of the embryo: mesoderm, ectoderm, and endoderm. In this chapter, we focus on the first phase of gastrulation in Drosophila involving patterning of early embryos when cells differentiate their gene expression programs. This patterning process requires coordination of multiple developmental processes including genome reprogramming at the maternal-to-zygotic transition, combinatorial action of transcription factors to support distinct gene expression, and dynamic feedback between this genetic patterning by transcription factors and changes in cell morphology. We discuss the gene regulatory programs acting during patterning to specify the three germ layers, which involve the regulation of spatiotemporal gene expression coupled to physical tissue morphogenesis.
Topics: Animals; Body Patterning; Drosophila Proteins; Drosophila melanogaster; Embryo, Nonmammalian; Gastrula; Gastrulation; Gene Expression Regulation, Developmental; Signal Transduction; Transcription Factors; Zygote
PubMed: 31959292
DOI: 10.1016/bs.ctdb.2019.11.004 -
Cell and Tissue Research Jan 2016The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA... (Review)
Review
The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment and in the identification of other functions of the ORC proteins. Together with expected localizations to the chromatin during G1, we found an unexpected distribution in the cytoplasm that appeared to accumulate ORC proteins suggesting potential roles for ORC subunits in mitosis and chromatin segregation. ORC1, 2, 3, and 5 all localize to the area between the separating maternal chromosomes shortly after fertilization. ORC4 forms a cage around the set of chromosomes that will be extruded during polar body formation before it binds to the chromatin shortly before zygotic DNA replication. These data suggest that the ORC proteins may also play roles in preparing the cell for DNA replication in addition to their direct role in establishing functional replication origins.
Topics: Animals; DNA Replication; Female; Humans; Male; Origin Recognition Complex; Spermatozoa; Zygote
PubMed: 26453397
DOI: 10.1007/s00441-015-2296-3 -
Cellular and Molecular Life Sciences :... May 2018The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest... (Review)
Review
The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest stages of embryogenesis, including maternal component (mRNAs and proteins) degradation and zygotic genome activation (ZGA). Various protein post-translational modifications have been identified during the MZT, such as phosphorylation, methylation and ubiquitination. Precise post-translational regulation mechanisms are essential for the timely transition of early embryonic development. In this review, we summarize recent progress regarding the molecular mechanisms underlying post-translational regulation of maternal component degradation and ZGA during the MZT and discuss some important issues in the field.
Topics: Animals; Embryonic Development; Female; Gene Expression Regulation, Developmental; Humans; Pregnancy; Protein Processing, Post-Translational; RNA, Messenger, Stored; Zygote
PubMed: 29427077
DOI: 10.1007/s00018-018-2750-y -
JBRA Assisted Reproduction May 2020The mitochondria are intracellular organelles, and just like the cell nucleus they have their own genome. They are extremely important for normal body functioning and... (Review)
Review
The mitochondria are intracellular organelles, and just like the cell nucleus they have their own genome. They are extremely important for normal body functioning and are responsible for ATP production - the main energy source for the cell. Mitochondrial diseases are associated with mutations in mitochondrial DNA and are inherited exclusively from the mother. They can affect organs that depend on energy metabolism, such as skeletal muscles, the cardiac system, the central nervous system, the endocrine system, the retina and liver, causing various incurable diseases. Mitochondrial replacement techniques provide women with mitochondrial defects a chance to have normal biological children. The goal of such treatment is to reconstruct functional oocytes and zygotes, in order to avoid the inheritance of mutated genes; for this the nuclear genome is withdrawn from an oocyte or zygotes, which carries mitochondrial mutations, and is implanted in a normal anucleated cell donor. Currently, the options of a couple to prevent the transmission of mitochondrial diseases are limited, and mitochondrial donation techniques provide women with mitochondrial defects a chance to have normal children. The nuclear genome can be transferred from oocytes or zygotes using techniques such as pronuclear transfer, spindle transfer, polar body transfer and germinal vesicle transfer. This study presents a review of developed mitochondrial substitution techniques, and its ability to prevent hereditary diseases.
Topics: Adult; DNA, Mitochondrial; Female; Genome, Mitochondrial; Humans; Male; Mitochondrial Diseases; Mitochondrial Replacement Therapy; Mutation; Oocytes; Parents; Zygote
PubMed: 32073245
DOI: 10.5935/1518-0557.20190086 -
Cold Spring Harbor Perspectives in... Nov 2015Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of... (Review)
Review
Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.
Topics: Adult Stem Cells; Animals; Blastocyst; Cell Communication; Cell Differentiation; DNA Methylation; Embryonic Development; Epigenomics; Genomic Imprinting; Histones; Oocytes; Pluripotent Stem Cells; Zygote
PubMed: 26525151
DOI: 10.1101/cshperspect.a019422 -
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 -
Biochemical Society Transactions Nov 2021In somatic cells, RNA polymerase II (Pol II) transcription initiation starts by the binding of the general transcription factor TFIID, containing the TATA-binding... (Review)
Review
In somatic cells, RNA polymerase II (Pol II) transcription initiation starts by the binding of the general transcription factor TFIID, containing the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs), to core promoters. However, in growing oocytes active Pol II transcription is TFIID/TBP-independent, as during oocyte growth TBP is replaced by its vertebrate-specific paralog TBPL2. TBPL2 does not interact with TAFs, but stably associates with TFIIA. The maternal transcriptome is the population of mRNAs produced and stored in the cytoplasm of growing oocytes. After fertilization, maternal mRNAs are inherited by the zygote from the oocyte. As transcription becomes silent after oocyte growth, these mRNAs are the sole source for active protein translation. They will participate to complete the protein pool required for oocyte terminal differentiation, fertilization and initiation of early development, until reactivation of transcription in the embryo, called zygotic genome activation (ZGA). All these events are controlled by an important reshaping of the maternal transcriptome. This procedure combines cytoplasmic readenylation of stored transcripts, allowing their translation, and different waves of mRNA degradation by deadenylation coupled to decapping, to eliminate transcripts coding for proteins that are no longer required. The reshaping ends after ZGA with an almost total clearance of the maternal transcripts. In the past, the murine maternal transcriptome has received little attention but recent progresses have brought new insights into the regulation of maternal mRNA dynamics in the mouse. This review will address past and recent data on the mechanisms associated with maternal transcriptome dynamic in the mouse.
Topics: Animals; Embryonic Development; Female; Gene Expression Regulation, Developmental; Mice; Nuclear Proteins; Oocytes; Pregnancy; Promoter Regions, Genetic; RNA Polymerase II; RNA Stability; RNA, Messenger; TATA Box Binding Protein-Like Proteins; TATA-Box Binding Protein; Transcription, Genetic; Transcriptome; Zygote
PubMed: 34415300
DOI: 10.1042/BST20201125 -
Developmental Cell Aug 2018Parental genomes are initially separate in the zygote following fertilization. A recent study in Science by Reichmann et al. (2018) reveals that dual spindles assemble...
Parental genomes are initially separate in the zygote following fertilization. A recent study in Science by Reichmann et al. (2018) reveals that dual spindles assemble around the two pronuclei in mouse embryos to maintain separation of the two parental genomes through the first zygotic division.
Topics: Animals; Cell Nucleus; Fertilization; Genome; Mice; Zygote
PubMed: 30086299
DOI: 10.1016/j.devcel.2018.07.019 -
Cellular and Molecular Life Sciences :... Jan 2020Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is... (Review)
Review
Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is ancestral to all extant eukaryotes. Although sexual development is extremely diverse, common molecular elements have been retained. HAP2-GCS1, a protein that promotes the fusion of gamete cell membranes that is related in structure to certain viral fusogens, is conserved in many eukaryotic lineages, even though gametes vary considerably in form and behaviour between species. Similarly, although zygotes have dramatically different forms and fates in different organisms, diverse eukaryotes share a common developmental programme in which homeodomain-containing transcription factors play a central role. These common mechanistic elements suggest possible common evolutionary histories that, if correct, would have profound implications for our understanding of eukaryogenesis.
Topics: Animals; Biological Evolution; Cell Membrane; Eukaryota; Germ Cells; Phylogeny; Transcription Factors; Zygote
PubMed: 31203379
DOI: 10.1007/s00018-019-03187-1