Special Issue "The Early Mouse Embryo as a Model Organism for Reprogramming"

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Technologies and Resources for Genetics (including Tools, Software and Databases)".

Deadline for manuscript submissions: closed (15 January 2011)

Special Issue Editor

Guest Editor
Dr. Mylene W. M. Yao

Stanford University School of Medicine, Department of Ob/GYN, Division of Reproductive Endocrinology and Infertility, 300 Pasteur Drive, MC: 5317, Stanford, CA 94305-5317, USA
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Special Issue Information

Dear Colleagues,

I am very happy that Genes is preparing a special issue dedicated to pre-implantation embryo development. Not only is this topic a fascinating area in developmental biology, but unraveling its mysteries will prove to be a critical milestone in understanding a full spectrum of human developmental and clinical diseases, ranging from infertility and miscarriage to birth defects and early embryonic origins of adult diseases. In this issue, we will focus on requirements of embryo development -- whether genetic, epigenetic, environmental or an combination thereof -- and how perturbations may affect embryo viability and development.

After fertilization, the early embryo advances through developmental stages until blastocyst formation. The highly differentiated egg and sperm fuse to form the zygote (also known as the 1-cell or 2-pronuclei stage embryo), which then undergoes dramatic reprogramming during the 2-cell, 4-cell, multi-cell, compaction and blastocyst stages. The blastocyst represents a critical developmental milestone, because cells resulting from the first lineage-specific differentiation - the inner cell mass (ICM) and trophectoderm - are morphologically distinct. The ICM gives rise to the developing fetus in vivo, and pluripotent embryonic stem cells (ESCs)in vitro; the trophectoderm gives rise to the placenta. Thus, the early embryo is a powerful "model organism" for studying requirements and factors influencing lineage-specific differentiation. The early embryo model also serves a special role for studying pluripotency and reprogramming, as it hosts a reprogramming toolkit that has withstood the tests of Nature.

Unraveling the mysteries of early embryo development poses challenges that are often best tackled by asking very fundamental questions and taking a creative, interdisciplinary approach. Here, we will highlight novel experimental paradigms and discoveries that have been unveiled for the early mammalian embryo.

Enjoy!

Dr. Mylene W. M. Yao
Guest Editor

Keywords

  • embryo
  • preimplantation
  • reprogramming
  • pluripotency
  • lineage-specific differentiation
  • inner cell mass
  • trophectoderm

Published Papers (6 papers)

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Research

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Open AccessArticle Effect of Culture Conditions on Viability of Mouse and Rat Embryos Developed in Vitro
Genes 2011, 2(2), 332-344; doi:10.3390/genes2020332
Received: 14 January 2011 / Revised: 11 February 2011 / Accepted: 29 March 2011 / Published: 1 April 2011
Cited by 6 | PDF Full-text (214 KB) | HTML Full-text | XML Full-text
Abstract
Currently in vitro culture of mouse preimplantation embryos has become a very important technique to investigate different mechanisms of early embryogenesis. However, there is a big difference in the preimplantation development between mammalian species. Despite close relatedness to mice, in vitro cultivation of
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Currently in vitro culture of mouse preimplantation embryos has become a very important technique to investigate different mechanisms of early embryogenesis. However, there is a big difference in the preimplantation development between mammalian species. Despite close relatedness to mice, in vitro cultivation of rat preimplantation embryos is still delicate and needs further investigation and optimizations. In this study we have compared the in vitro developmental potential of mouse and rat embryos cultured at different culture conditions in parallel experiments. Interestingly, mouse zygotes developed in vitro until blastocyst stage even in inadequate medium without any phosphates and with low osmolarity which was formulated especially for cultivation of rat embryos. Rat parthenotes and zygotes developed in M16 medium formulated for mouse embryos only till 2-cell stage and further development is blocked completely at this stage. Moreover, developmental ability of rat embryos in vitro was significantly lower in comparison with mouse even in special rat mR1ECM medium. Mouse and rat embryos at 2-cell stage obtained in vivo developed until blastocyst stages significantly more efficiently compared to zygotes. Culture of mouse zygotes in glass capillaries resulted in a significantly higher rate of morula and blastocyst development compared with dishes. The Well-of-the-Well system resulted in a significant improvement when compared with dishes for the culture of rat zygotes only until morula stage. Reduced oxygen tension increased the developmental rate of rat but not mouse zygotes until blastocyst stage. This study demonstrates that development of early preimplantation embryos is altered by different culture conditions and show strong differences even between two related species such as mice and rats. Therefore, for understanding the fundamental mechanisms of early mammalian development it is very important to use embryos of various species. Full article
(This article belongs to the Special Issue The Early Mouse Embryo as a Model Organism for Reprogramming)
Open AccessArticle Hes1 Oscillations Contribute to Heterogeneous Differentiation Responses in Embryonic Stem Cells
Genes 2011, 2(1), 219-228; doi:10.3390/genes2010219
Received: 17 December 2010 / Revised: 12 February 2011 / Accepted: 13 February 2011 / Published: 22 February 2011
Cited by 11 | PDF Full-text (94 KB) | HTML Full-text | XML Full-text
Abstract
Embryonic stem (ES) cells can differentiate into multiple types of cells belonging to all three germ layers. Although ES cells are clonally established, they display heterogeneous responses upon the induction of differentiation, resulting in a mixture of various types of differentiated cells. Our
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Embryonic stem (ES) cells can differentiate into multiple types of cells belonging to all three germ layers. Although ES cells are clonally established, they display heterogeneous responses upon the induction of differentiation, resulting in a mixture of various types of differentiated cells. Our recent reports have shown that Hes1 regulates the fate choice of ES cells by repressing Notch signaling, and that the oscillatory expression of Hes1 contributes to various differentiation responses in ES cells. Here we discuss the mechanism regulating the intracellular dynamics in ES cells and how to trigger the lineage choice from pluripotent ES cells. Full article
(This article belongs to the Special Issue The Early Mouse Embryo as a Model Organism for Reprogramming)

Review

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Open AccessReview Understanding the Molecular Circuitry of Cell Lineage Specification in the Early Mouse Embryo
Genes 2011, 2(3), 420-448; doi:10.3390/genes2030420
Received: 2 June 2011 / Revised: 24 June 2011 / Accepted: 5 July 2011 / Published: 13 July 2011
Cited by 7 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text
Abstract
Pluripotent stem cells hold great promise for cell-based therapies in regenerative medicine. However, critical to understanding and exploiting mechanisms of cell lineage specification, epigenetic reprogramming, and the optimal environment for maintaining and differentiating pluripotent stem cells is a fundamental knowledge of how these
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Pluripotent stem cells hold great promise for cell-based therapies in regenerative medicine. However, critical to understanding and exploiting mechanisms of cell lineage specification, epigenetic reprogramming, and the optimal environment for maintaining and differentiating pluripotent stem cells is a fundamental knowledge of how these events occur in normal embryogenesis. The early mouse embryo has provided an excellent model to interrogate events crucial in cell lineage commitment and plasticity, as well as for embryo-derived lineage-specific stem cells and induced pluripotent stem (iPS) cells. Here we provide an overview of cell lineage specification in the early (preimplantation) mouse embryo focusing on the transcriptional circuitry and epigenetic marks necessary for successive differentiation events leading to the formation of the blastocyst. Full article
(This article belongs to the Special Issue The Early Mouse Embryo as a Model Organism for Reprogramming)
Open AccessReview A Reverse Transcriptase-Dependent Mechanism Is Essential for Murine Preimplantation Development
Genes 2011, 2(2), 360-373; doi:10.3390/genes2020360
Received: 6 April 2011 / Revised: 6 May 2011 / Accepted: 10 May 2011 / Published: 18 May 2011
Cited by 5 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
LINE-1 (Long Interspersed Nuclear elements) and HERVs (Human Endogenous Retroviruses) are two families of retrotransposons which together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly that encoding the reverse transcriptase (RT) enzyme, are generally expressed
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LINE-1 (Long Interspersed Nuclear elements) and HERVs (Human Endogenous Retroviruses) are two families of retrotransposons which together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly that encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is up-regulated in embryonic tissues and transformed cells. Here we review evidence indicating that the LINE-1-encoded RT plays regulatory roles in early embryonic development. Indeed, antisense-mediated inhibition of expression of a highly expressed LINE-1 family in mouse zygotes caused developmental arrest at the two- or four-cell embryo stages. Development is also arrested when the embryo endogenous RT activity is pharmacologically inhibited by nevirapine, an RT inhibitor currently employed in AIDS treatment. The arrest of embryonic development is irreversible even after RT inhibition is removed and it is associated with subverted gene expression profiles. These data indicate an early requirement for LINE-1-encoded RT to support early developmental progression. Consistent with this, recent findings indicate that a reverse transcription wave is triggered in the zygote a few hours after fertilization and is propagated at least through the first two rounds of cell division. On the whole these findings suggest that reverse transcription is strictly required in early embryos as a key component of a novel RT-dependent mechanism that regulated the proper unfolding of the developmental program. Full article
(This article belongs to the Special Issue The Early Mouse Embryo as a Model Organism for Reprogramming)
Open AccessReview Post-Transcriptional Control of Gene Expression in Mouse Early Embryo Development: A View from the Tip of the Iceberg
Genes 2011, 2(2), 345-359; doi:10.3390/genes2020345
Received: 25 January 2011 / Revised: 22 February 2011 / Accepted: 2 April 2011 / Published: 6 April 2011
Cited by 2 | PDF Full-text (308 KB) | HTML Full-text | XML Full-text
Abstract
Fertilization is a very complex biological process that requires the perfect cooperation between two highly specialized cells: the male and female gametes. The oocyte provides the physical space where this process takes place, most of the energetic need, and half of the genetic
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Fertilization is a very complex biological process that requires the perfect cooperation between two highly specialized cells: the male and female gametes. The oocyte provides the physical space where this process takes place, most of the energetic need, and half of the genetic contribution. The spermatozoon mostly contributes the other half of the chromosomes and it is specialized to reach and to penetrate the oocyte. Notably, the mouse oocyte and early embryo are transcriptionally inactive. Hence, they fully depend on the maternal mRNAs and proteins stored during oocyte maturation to drive the onset of development. The new embryo develops autonomously around the four-cell stage, when maternal supplies are exhausted and the zygotic genome is activated in mice. This oocyte-to-embryo transition needs an efficient and tightly regulated translation of the maternally-inherited mRNAs, which likely contributes to embryonic genome activation. Full understanding of post-transcriptional regulation of gene expression in early embryos is crucial to understand the reprogramming of the embryonic genome, it might help driving reprogramming of stem cells in vitro and will likely improve in vitro culturing of mammalian embryos for assisted reproduction. Nevertheless, the knowledge of the mechanism(s) underlying this fundamental step in embryogenesis is still scarce, especially if compared to other model organisms. We will review here the current knowledge on the post-transcriptional control of gene expression in mouse early embryos and discuss some of the unanswered questions concerning this fascinating field of biology. Full article
(This article belongs to the Special Issue The Early Mouse Embryo as a Model Organism for Reprogramming)
Open AccessReview Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development
Genes 2011, 2(2), 298-312; doi:10.3390/genes2020298
Received: 14 January 2011 / Revised: 8 March 2011 / Accepted: 21 March 2011 / Published: 24 March 2011
PDF Full-text (261 KB) | HTML Full-text | XML Full-text
Abstract
Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently,
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Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development. Full article
(This article belongs to the Special Issue The Early Mouse Embryo as a Model Organism for Reprogramming)

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