IGF-2 receptors are first expressed at the 2-cell stage of mouse development

M.B. Harvey; P.L. Kaye

doi:10.1242/dev.111.4.1057

IGF-2 receptors are first expressed at the 2-cell stage of mouse development

Development ◽

10.1242/dev.111.4.1057 ◽

1991 ◽

Vol 111 (4) ◽

pp. 1057-1060

Author(s):

M.B. Harvey ◽

P.L. Kaye

Keyword(s):

Preimplantation Development ◽

Mouse Development ◽

Cell Stage ◽

Receptor Mrna ◽

Embryonic Genome

A specific IGF-2 receptor antiserum was used to reveal the presence of IGF-2 receptors during preimplantation development of mice. Receptors were present on 2-, 4- and 8-cell embryos, morulae, blastocysts, and on ICMs isolated prior to staining. There was no evidence for receptors on fertilized eggs. These observations confirm reports of the expression of IGF-2 receptor mRNA as early as the 2-cell stage and refine similar observations in blastocysts to confirm expression in both the TE and ICM. A potential auto/paracrine loop is thus one of the first products of activation of the embryonic genome and is expressed constitutively through preimplantation development.

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131DIFFERENTIAL DNA METHYLATION CHANGES OF THE REPETITIVE SEQUENCES DURING PREIMPLANTATION DEVELOPMENT IN THE MOUSE

Reproduction Fertility and Development ◽

10.1071/rdv16n1ab131 ◽

2004 ◽

Vol 16 (2) ◽

pp. 188

Author(s):

S.-H. Kim ◽

Y.-K. Kang ◽

D.-B. Koo ◽

M.-J. Kang ◽

K.-K. Lee ◽

...

Keyword(s):

Dna Sequences ◽

Repetitive Sequences ◽

Dna Demethylation ◽

Preimplantation Development ◽

Mouse Development ◽

Cell Stage ◽

Paternal Genome ◽

Satellite Sequences ◽

Centromeric Satellite ◽

Morula Stage

DNA demethylation as an epigenetic change is a unique event genome-wide, occurring at preimplantation and germ cell stages during mouse development. The paternal genome after fertilization is demethylated first, referred to active demethylation, followed by demethylation of the maternal genome during preimplantation development in the mouse. To examine methylation changes in the early mouse embryo, methylation states of various genomic regions such as intracisternal A-particle (IAP), early retrotransposon (Etn) and centromeric satellite sequences were determined by means of a bisulfite sequencing method. For methylation analysis, genomic DNA was first isolated from each developmental stage of embryo (about 300 cells in total), respectively, and exposed to 1.9M sodium bisulfite overnight. Targeted DNA sequences were amplified from bisulfite-treated genomic DNAs by PCR, cloned into pGEM T-easy vector and sequenced. Results indicated that IAP sequences maintained high levels of methylation until the morula stage and were demethylated in blastocysts. In contrast to the IAP sequences, methylation states of Etn elements were remarkably erased after fertilization, completely demethylated at the 8-cell stage and then remethylated at the morula stage. Centromeric satellite sequences showed low methylation states throughout all preimplantation stages of embryos, indicating that the satellite sequences are substantially demethylated in both paternal and maternal genomes. The results suggest that differential epifenetic changes among the repetitive sequences may be responsible for peculiar chromatin structure of respective genomic loci and/or may regulate gene expression during preimplantation development in the mouse.

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Involvement of oocyte-coded message in cell differentiation control of early human embryos

Development ◽

10.1242/dev.105.2.317 ◽

1989 ◽

Vol 105 (2) ◽

pp. 317-322 ◽

Cited By ~ 1

Author(s):

J. Tesarik

Keyword(s):

Plasma Membrane ◽

Cell Mass ◽

Preimplantation Development ◽

Gene Activity ◽

Cell Junctions ◽

Preimplantation Embryos ◽

Embryonic Cells ◽

Cell Stage ◽

Continuous Increase ◽

Embryonic Genome

Considerable evidence indicates that the first phenotypical diversification of embryonic cells during mammalian preimplantation development is achieved in two successive steps: (i) generation of cell asymmetry and (ii) unequal cell division. This paper shows that ultrastructural signs of blastomere surface regionalization in human preimplantation embryos are evident as early as the 2-cell stage when modifications of the plasma membrane (loss of microvilli and endocytotic activity, formation of cell junctions) are induced in places of blastomere contact. The capacity of the plasma membrane to undergo these cell-contact-dependent changes precedes any detectable activity of the embryonic genome. The area of the modified plasma membrane shows a continuous increase during the first three cleavage stages. The progression of these membrane modifications is the same in embryos that have properly enhanced their transcriptional activity at the 8-cell stage and in those that have not. In spite of the failure of this early-cleavage-progressed-cleavage transition of gene activity, the formation of zonula adherens and gap junctions goes on apparently normally in the respective embryos and morphologically distinct inner cell mass and trophectoderm cell lineages are subsequently segregated in 16-cell morulae. However, tight junctions do not develop under these conditions. The occurrence of the progressed-cleavage pattern of gene activity in the majority of embryonic cells is a necessary prerequisite for the appearance of the blastocyst cavity. Thus, oocyte-coded message is apparently involved in the control of relatively late stages of human preimplantation development including the differentiation of the first two embryonic tissues, but the embryonic genome is required for the full achievement of this early differentiative event.

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Expression profile of protein kinase C isozymes in preimplantation mouse development

Reproduction ◽

10.1530/rep.1.00571 ◽

2005 ◽

Vol 130 (4) ◽

pp. 441-451 ◽

Cited By ~ 13

Author(s):

Hesam Dehghani ◽

Ann C Hahnel

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Mouse Embryo ◽

Mitotic Cell ◽

Preimplantation Development ◽

Mouse Development ◽

Cell Stage ◽

Kinase C ◽

Preimplantation Mouse ◽

The Individual

In the preimplantation mouse embryo, the protein kinase C (PKC) family has been implicated in regulation of egg activation, progression of meiotic and mitotic cell cycles, embryo compaction, and blastulation, but the involvement of the individual isozymes is largely unknown. Here, using semiquantitative immunocytochemistry and confocal microscopy we analyze the relative amount and subcellular distribution of ten isozymes of PKC (α, βI, βII, γ, δ, ε, η, 𝛉, ζ, ι/λ) and a PKC-anchoring protein, receptor for activated C-kinase 1 (RACK1). Our results show that all of these isoforms of PKC are present between the two-cell and blastocyst stages of mouse preimplantation development, and that each has a distinct, dynamic pattern and level of expression. The data suggest that different complements of the isozymes are involved in various steps of preimplantation development, and will serve as a framework for further functional studies of the individual isozymes. In particular, there was a transient increase in the nuclear concentration of several isozymes at the early four-cell stage, suggesting that some of the PKC isozymes might be involved in regulation of nuclear organization and function in the early mouse embryo.

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Essential role of paternal chromatin in the regulation of transcriptional activity during mouse preimplantation development

Reproduction ◽

10.1530/rep-10-0109 ◽

2011 ◽

Vol 141 (1) ◽

pp. 67-77 ◽

Cited By ~ 20

Author(s):

Hong-Thuy Bui ◽

Sayaka Wakayama ◽

Eiji Mizutani ◽

Keun-Kyu Park ◽

Jin-Hoi Kim ◽

...

Keyword(s):

Transcriptional Activity ◽

Preimplantation Development ◽

Cell Stage ◽

Male And Female ◽

Embryonic Genome ◽

Preimplantation Mouse Embryo ◽

Sperm Development ◽

Preimplantation Mouse ◽

Nascent Rna ◽

Androgenetic Embryos

Several lines of evidence indicate that the formation of a transcriptionally repressive state during the two-cell stage in the preimplantation mouse embryo is superimposed on the activation of the embryonic genome. However, it is difficult to determine the profile of newly synthesized (nascent) RNA during this phase because large amounts of maternal RNA accumulate in maturing oocytes to support early development. Using 5-bromouridine-5′-triphosphate labeling of RNA, we have verified that nascent RNA synthesis was repressed between the two-cell and four-cell transition in normally fertilized but not in parthenogenetic embryos. Moreover, this repression was contributed by sperm (male) chromatin, which we confirmed by studying androgenetic embryos. The source of factors responsible for repressing nascent RNA production was investigated using different stages of sperm development. Fertilization with immature round spermatids resulted in a lower level of transcriptional activity than with ICSI at the two-cell stage, and this was consistent with further repression at the four-cell stage in the ICSI group. Finally, study on DNA replication and chromatin remodeling was performed using labeled histones H3 and H4 to differentiate between male and female pronuclei. The combination of male and female chromatin appeared to decrease nascent RNA production in the fertilized embryo. This study indicates that paternal chromatin is important in the regulation of transcriptional activity during mouse preimplantation development and that this capacity is acquired during spermiogenesis.

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Bovine preimplantation embryos with silenced nucleophosmin mRNA are able to develop until the blastocyst stage

Reproduction ◽

10.1530/rep-12-0033 ◽

2012 ◽

Vol 144 (3) ◽

pp. 349-359 ◽

Cited By ~ 3

Author(s):

Tereza Toralová ◽

Veronika Benešová ◽

Kateřina Vodičková Kepková ◽

Petr Vodička ◽

Andrej Šušor ◽

...

Keyword(s):

Ribosome Biogenesis ◽

Blastocyst Stage ◽

Preimplantation Development ◽

Developmental Competence ◽

Preimplantation Embryos ◽

Bovine Embryo ◽

Cell Stage ◽

Embryonic Genome ◽

Genome Activation

This study was conducted to investigate the effect of silencing nucleophosmin in the development of in vitro-produced bovine embryos. Nucleophosmin is an abundant multifunctional nucleolar phosphoprotein that participates, for example, in ribosome biogenesis or centrosome duplication control. We showed that although the transcription of embryonic nucleophosmin started already at late eight-cell stage, maternal protein was stored throughout the whole preimplantation development and was sufficient for the progression to the blastocyst stage. At the beginning of embryogenesis, translation occurs on maternally derived ribosomes, the functionally active nucleoli emerge during the fourth cell cycle in bovines. We found that nucleophosmin localisation reflected the nucleolar formation during bovine preimplantation development. The protein was detectable from the beginning of embryonic development. Before embryonic genome activation, it was dispersed throughout the nucleoplasm. The typical nucleolar localisation emerged with the formation of active nucleoli. At the blastocyst stage, nucleophosmin tended to localise especially to the trophectoderm. To see for how long is maternal nucleophosmin preserved, we silenced the nucleophosmin mRNA using RNA interference approach. Although a large portion of nucleophosmin was degraded in embryos with silenced nucleophosmin mRNA, an amount sufficient for normal development was preserved and we detected only a temporal delay in nucleophosmin relocalisation to nucleoli. Moreover, we observed no defects in nuclear shape or cytoskeleton previously found in somatic cells and only a non-significant decrease in embryonic developmental competence. Thus, our results show that the preserved amount of maternal nucleophosmin is sufficient for preimplantation development of bovine embryo.

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Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice

Reproduction ◽

10.1530/rep-16-0277 ◽

2016 ◽

Vol 152 (5) ◽

pp. 417-430 ◽

Cited By ~ 10

Author(s):

Atsushi Fukuda ◽

Atsushi Mitani ◽

Toshiyuki Miyashita ◽

Hisato Kobayashi ◽

Akihiro Umezawa ◽

...

Keyword(s):

Nuclear Localization ◽

Splice Variants ◽

Protein Localization ◽

Preimplantation Development ◽

Preimplantation Embryos ◽

Sequencing Analysis ◽

Dependent Manner ◽

Cell Stage ◽

Protein Levels ◽

Oct4 Protein

Spatiotemporal expression of transcription factors is crucial for genomic reprogramming. Pou5f1 (Oct4) is an essential transcription factor for reprogramming. A recent study reported that OCT4A, which is crucial for establishment and maintenance of pluripotent cells, is expressed in oocytes, but maternal OCT4A is dispensable for totipotency induction. Whereas another study reported that OCT4B, which is not related to pluripotency, is predominantly expressed instead of OCT4A during early preimplantation phases in mice. To determine the expression states of OCT4 in murine preimplantation embryos, we conducted in-depth expression and functional analyses. We found that pluripotency-related OCT4 mainly localizes to the cytoplasm in early preimplantation phases, with no major nuclear localization until the 8–16-cell stage despite high expression in both oocytes and early embryos. RNA-sequencing analysis using oocytes and early preimplantation embryos could not identify the splice variants creating alternative forms of OCT4 protein. Forced expression of OCT4 in zygotes by the injection of polyadenylated mRNA clearly showed nuclear localization of OCT4 protein around 3–5-fold greater than physiological levels and impaired developmental competency in a dose-dependent manner. Embryos with modest overexpression of OCT4 could develop to the 16-cell stage; however, more than 50% of the embryos were arrested at this stage, similar to the results for OCT4 depletion. In contrast, extensive overexpression of OCT4 resulted in complete arrest at the 2-cell stage accompanied by downregulation of zygotically activated genes and repetitive elements related to the totipotent state. These results demonstrated that OCT4 protein localization was spatiotemporally altered during preimplantation development, and strict control of Oct4 protein levels was essential for proper totipotential reprogramming.

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Expression of the HSP 70.1 gene, a landmark of early zygotic activity in the mouse embryo, is restricted to the first burst of transcription

Development ◽

10.1242/dev.121.1.113 ◽

1995 ◽

Vol 121 (1) ◽

pp. 113-122 ◽

Cited By ~ 4

Author(s):

E. Christians ◽

E. Campion ◽

E.M. Thompson ◽

J.P. Renard

Keyword(s):

Dna Replication ◽

Mouse Embryo ◽

Culture Conditions ◽

Hsp 70 ◽

Cell Stage ◽

Embryonic Genome ◽

Genome Activation ◽

Alpha Amanitin ◽

Zygotic Genome

Activation of the mouse embryonic genome at the 2-cell stage is characterized by the synthesis of several alpha-amanitin-sensitive polypeptides, some of which belong to the multigenic hsp 70 family. In the present work we show that a member of this family, the HSP 70.1 gene, is highly transcribed at the onset of zygotic genome activation. Transcription of this gene began as early as the 1-cell stage. Expression of the gene continued through the early 2-cell stage but was repressed before the completion of the second round of DNA replication. During this period we observed that the level of transcription was modulated by in vitro culture conditions. The coincidence of repression of HSP70.1 transcription with the second round of DNA replication was not found for other transcription-dependent polypeptides synthesized at the 2-cell stage.

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Cell division and cell allocation in early mouse development

Development ◽

10.1242/dev.48.1.37 ◽

1978 ◽

Vol 48 (1) ◽

pp. 37-51

Author(s):

S. J. Kelly ◽

J. G. Mulnard ◽

C. F. Graham

Keyword(s):

Cell Division ◽

Tritiated Thymidine ◽

Mouse Embryos ◽

Mouse Development ◽

Stages Of Development ◽

Cell Stage ◽

Cell Cycles ◽

Short Cell ◽

Early Mouse

Cell division was observed in intact and dissociated mouse embryos between the 2-cell stage and the blastocyst in embryos developing in culture. Division to the 4-cell stage was usually asynchronous. The first cell to divide to the 4-cell stage produced descendants which tended to divide ahead of those cells produced by its slow partner at all subsequent stages of development up to the blastocyte stage. The descendants of the first cell to divide to the 4-cell stage did not subsequently have short cell cycles. The first cell or last cell to divide from the 4-cell stage was labelled with tritiated thymidine. The embryo was reassembled, and it was found that the first pair of cells to reach the 8-cell stage contributed disproportionately more descendants to the ICM when compared with the last cell to divide to the 8-cell stage.

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Synthesis and phosphorylation of uvomorulin during mouse early development

Development ◽

10.1242/dev.115.1.313 ◽

1992 ◽

Vol 115 (1) ◽

pp. 313-318 ◽

Cited By ~ 2

Author(s):

M. Sefton ◽

M.H. Johnson ◽

L. Clayton

Keyword(s):

Cell Adhesion ◽

Early Development ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Blastocyst Stage ◽

Embryonic Stage ◽

Cell Stage ◽

Mouse Oocytes ◽

Maternal Mrna ◽

Embryonic Genome

The cell adhesion molecule, uvomorulin, is synthesised in both the 135 × 10(3) M(r) precursor and 120 × 10(3) M(r) mature forms on maternal mRNA templates in unfertilized and newly fertilized mouse oocytes. Synthesis on maternal message ceases during the 2-cell stage to resume later on mRNA encoded presumptively by the embryonic genome. Uvomorulin is detectable by immunoblotting at all stages upto the blastocyst stage, but shows variations in its total amount and processing with embryonic stage. Whilst only trace levels of phosphorylated uvomorulin are detectable in early and late 4-cell embryos, uvomorulin in 8-cell embryos is phosphorylated.

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