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

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
E-Mail: mylene.yao@stanford.edu

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

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

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

Type of Paper: Review
Title: Role of Endogenous Reverse Transcriptase in Early Murine Preimplantation Development
Authors: P. Vitullo, I. Sciamanna, A. Curatolo and C. Spadafora
Affiliation: Istituto Superiore di Sanità (Italian National Health Institute), Rome, Italy; E-Mail: corrado.spadafora@iss.it (C.S.)
Abstract: In mammalian cells, endogenous reverse transcriptase (RT) is encoded by two families of retrotransposons, i.e. LINE-1 (Long Interspersed Nuclear Elements) and endogenous retroviruses (ERVs). Growing evidence from our laboratory suggest that LINE-1-encoded RT plays regulatory roles in early embryonic development. We have found that inhibiting the expression of a family of highly expressed LINE-1 elements, obtained by microinjecting LINE-1 antisense oligonucleotides into mouse zygotes, causes developmental arrest at 2- or 4-cell stages. A similar arrest was observed when the endogenous RT activity was inhibited in embryos exposed to nevirapine, a pharmacological RT inhibitor currently employed in AIDS treatment. The arrest of embryo developmental progression, by either drug- or antisensense-mediated RT inhibition, was irreversible and was associated with subverted gene expression profiles. We propose that embryonic RT activity is absolutely required for proper unfolding of the developmental program.

Type of Paper: Review
Title: Molecular factors influencing the differentiation of midbrain dopamine neurons
Author: Isabel Liste
Affiliation: Instituto de Salud Carlos III, Centro Nacional de Microbiología, Área de Biología Celular y del Desarrollo, Madrid, Spain; E-Mail: iliste@cbm.uam.es
Abstract: Dopaminergic neurons in the midbrain (mDNs) play a central role in the regulation of voluntary movement as well as other complex behaviours, and their loss is associated with Parkinson`s disease (PD). Recent research in vertebrate development and genetics has identified a set of genetic cascades that underlie patterning and specification of mDNs as well as a number of factors that may facilitate this process. In parallel, rapid progress has been made in the generation of DNs from different types of stem cells and the development of stem cell-based therapies for PD. In this review I will focus on recent advances on molecular factors involved in the generation and survival of mDNs and outline how this knowledge can be exploited to develop novel strategies for the generation of these neurons from pluripotent and multipotent stem cells.

Type of Paper: Article
Title: Effect of Culture Conditions on Viability of Mouse and Rat Embryos Developed In Vitro
Authors: E. Popova, M. Bader and A. Krivokharchenko
Affiliation: Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; E-Mail: mbader@mdc-berlin.de
Abstract: In vitro culture of mouse embryos has become the most popular model to study basic processes during early development. 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 still remains a methodological problem, which needs further investigation and optimization. In this study we have therefore compared the in vitro developmental viability of mouse and rat embryos cultured at different culture conditions in parallel experiments. Our results demonstrate that early development of embryos is altered by different culture media and oxygen tension showing strong differences between two closely related species.

Type of Paper: Review
Title: The Emergence of Pluripotent and Differentiated Lineages in the Early Mouse Embryo
Authors: Mary E. Donohoe ¹, Anna Bergsmedh ², Rebecca A. Hughes ¹ and Anna-Katerina Hadjantonakis ³
Affiliations: ¹ Burke Medical Research Institute, Weill Cornell Medical College, New York, USA
² Department of Genetic Medicine, Weill Cornell Medical College, New York, USA
3 Developmental Biology Program, Sloan-Kettering Institute, New York, USA; E-Mail: hadj@mskcc.org (A.-K.H.)
Abstract: Regenerative medicine holds the enormous potential for patients with diseases.  However to understand the mechanisms of lineage specification, epigenetic reprogramming, and optimal environment for maintaining pluripotent stem cells we must understand how these events occur in normal embryogenesis.  The early mouse embryo has provided an excellent model to study events crucial in development with regards to cell fate and behavior for embryo-derived stem cells and induced pluripotent stem (iPS) cells.  Here we provide and overview of lineage specification in the pre-implantation mouse including the transcriptional circuitry and epigenetic marks necessary for successive differentiation events.