Regulation of Cell Fate and Cell Behaviour During Primitive Endoderm Formation in the Early Mouse Embryo

Regulation of Cell Fate and Cell Behaviour During Primitive Endoderm Formation in the Early Mouse Embryo
Author: Nestor Saiz
Publisher:
Total Pages:
Release: 2012
Genre:
ISBN:

The preimplantation stages of mammalian development are dedicated to the differentiation of two extraembryonic epithelia, the trophectoderm (TE) and the primitive endoderm (PrE), and their segregation from the pluripotent embryonic lineage, the epiblast. The TE and PrE are responsible for implantation into the uterus and for producing the tissues that will support and pattern the epiblast as it develops into the foetus. PrE and epiblast are formed in a two step process that involves random cell fate specification, mediated by fibroblast growth factor (FGF) signalling, and cell sorting through several mechanisms. In the present work I have addressed aspects of both steps of this process. Chimaera assays showed that epiblast precursors transplanted onto a recipient embryo rarely differentiate into PrE, while PrE precursors are able to switch their identity and become epiblast. Transient stimulation or inhibition of the FGF4-ERK pathway in the chimaeras can modify the behaviour of these cells and restore the plasticity of epiblast precursors. This work shows that epiblast precursors are refractory to differentiation signals, thus ensuring the preservation of the embryonic lineage. I have also found that atypical Protein Kinase C (aPKC) is a marker of PrE cells and that pharmacological inhibition of aPKC impairs the segregation of PrE and epiblast precursors. Furthermore, it affects the survival of PrE cells and can alter the subcellular localisation of the PrE transcription factor GATA4. These data indicate aPKC plays a central role for the sorting of the PrE and epiblast populations and links cell position within the embryo to PrE maturation and survival. Lastly, I have found that aPKC can directly phosphorylate GATA4 in vitro. Knockdown of GATA4 affects cell position within the embryo, whereas aPKC knockdown reduces the number of GATA4-positive cells. These results indicate GATA4 plays an important role in cell sorting during preimplantation development and suggest phosphorylation by aPKC could determine its presence in the nuclei of PrE cells. My work, in the light of the current knowledge, supports a model where the earliest cell fate decisions during mammalian development depend on cellular interactions and not on inherited cell fate determinants. This robust mode of development underlies the plasticity of the preimplantation embryo and ensures the formation of the first mammalian cell lineages, critical for any further progression in mammalian development.

Manipulating the Mouse Embryo

Manipulating the Mouse Embryo
Author: Andras Nagy
Publisher: Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press
Total Pages: 784
Release: 2003
Genre: Science
ISBN:

Provides background information and detailed protocols for developing a mouse colony and using the animals in transgenic and gene-targeting experiments. The protocols list the animals, equipment, and reagents required and step-by-step procedures. Topics include in vitro culture of preimplantation embryos, surgical procedures, the production of chimeras, and the analysis of genome alterations. The third edition adds protocols for cloning mice, modifying embryonic stem cells, intracytoplasmic sperm injection, and cryopreservation of embryos.

Mouse Development

Mouse Development
Author: Jacek Z. Kubiak
Publisher: Springer Science & Business Media
Total Pages: 436
Release: 2012-08-23
Genre: Science
ISBN: 3642304060

The mouse is a perfect model organism to study mammalian, and thus indirectly also human, embryology. Most scientific achievements that have had an important impact on the understanding of basic mechanisms governing embryo development in humans, originated from mouse embryology. Stem cell research, which now offers the promise of regenerative medicine, began with the isolation and culture of mouse embryonic stem cells by Martin Evans (who received the Nobel Prize in medicine in 2007 for this achievement) and Matthew Kaufman. This book provides an overview of mouse development, spanning from oocytes before fertilization to the state-of-the-art description of embryonic and adult stem cells. The chapters, written by the leading specialists in the field, deal with the most recent discoveries in this extremely fast-developing area of research.

Stem Cells and the Future of Regenerative Medicine

Stem Cells and the Future of Regenerative Medicine
Author: Institute of Medicine
Publisher: National Academies Press
Total Pages: 112
Release: 2002-01-25
Genre: Science
ISBN: 0309170427

Recent scientific breakthroughs, celebrity patient advocates, and conflicting religious beliefs have come together to bring the state of stem cell researchâ€"specifically embryonic stem cell researchâ€"into the political crosshairs. President Bush's watershed policy statement allows federal funding for embryonic stem cell research but only on a limited number of stem cell lines. Millions of Americans could be affected by the continuing political debate among policymakers and the public. Stem Cells and the Future of Regenerative Medicine provides a deeper exploration of the biological, ethical, and funding questions prompted by the therapeutic potential of undifferentiated human cells. In terms accessible to lay readers, the book summarizes what we know about adult and embryonic stem cells and discusses how to go about the transition from mouse studies to research that has therapeutic implications for people. Perhaps most important, Stem Cells and the Future of Regenerative Medicine also provides an overview of the moral and ethical problems that arise from the use of embryonic stem cells. This timely book compares the impact of public and private research funding and discusses approaches to appropriate research oversight. Based on the insights of leading scientists, ethicists, and other authorities, the book offers authoritative recommendations regarding the use of existing stem cell lines versus new lines in research, the important role of the federal government in this field of research, and other fundamental issues.

Cell Movements

Cell Movements
Author: Dennis Bray
Publisher: Garland Science
Total Pages: 396
Release: 2001
Genre: Cells
ISBN: 9780815332824

This book vividly describes how complex and integrated movements can arise from the properties and behaviors of biological molecules. It provides a uniquely integrated account in which the latest findings from biophysics and molecular biology are put into the context of living cells. This second edition is updated throughout with recent advances in the field and has a completely revised and redrawn art program. The text is suitable for advanced undergraduates, graduate students, and for professionals wishing for an overview of this field.

Postimplantation Development in the Mouse

Postimplantation Development in the Mouse
Author: Derek J. Chadwick
Publisher: John Wiley & Sons
Total Pages: 326
Release: 2008-04-30
Genre: Science
ISBN: 047051423X

Examines the establishment of the germ layers and other cell lineages in the early embryo including details of cell movements during the beginning stages of primitive streak formation. Discusses patterns of gene expression during the development of such tissues as the limb bud, skeletal, muscle and the central nervous systems placing special emphasis on commitment to particular cell types. Although it concentrates on the mouse as an example of mammalian development--chick, amphibian and Drosophila embryogenesis are employed whenever these organisms are more applicable to the study of a particular problem.

Mammalian Development

Mammalian Development
Author: Peter Lonai
Publisher: CRC Press
Total Pages: 406
Release: 1996-09-01
Genre: Nature
ISBN: 9783718659203

"This book aims to provide a survey of the developmental biology of mammals--Pref.

Planar Cell Polarization during Development

Planar Cell Polarization during Development
Author: Marek Mlodzik
Publisher: Elsevier
Total Pages: 183
Release: 2005-08-02
Genre: Science
ISBN: 0080458610

Cellular polarization is key to all cellular functions. Our perceptions, which are derived from our senses, depend on the proper cellular polarization of our sense organs, such as the eyes or ears. Much of this book examines the different aspects in cellular polarization and its researched role in the Drosophila, where the first planar cellular polarity (PCP) gene was discovered over 20 years ago. Topics also include: From flies to man: how we are polarized, Marking an embryo work, Cellular polarization at its functional best, Hearing and seeing your environment, and From a cell to an organ. This series represents timely issues in developmental biology. It provides annual reviews of selected topics, written from the perspectives of leading investigators in the field of development. * Presents many various organisms such as flies, fish, frogs and mice * Offers over 40 exceptional illustrations * First of its kind to include new data and detailed models on cell planar polarization

Stem Cells in Reproductive Medicine

Stem Cells in Reproductive Medicine
Author: Carlos Simón
Publisher: Cambridge University Press
Total Pages: 199
Release: 2013-07-04
Genre: Medical
ISBN: 1107034477

Stem cell science has the potential to impact human reproductive medicine significantly - cutting edge technologies allow the production and regeneration of viable gametes from human stem cells offering potential to preciously infertile patients. Written by leading experts in the field Stem Cells in Reproductive Medicine brings together chapters on the genetics and epigenetics of both the male and female gametes as well as advice on the production and regeneration of gene cells in men and women, trophoblasts and endometrium from human embryonic and adult stem cells. Although focussing mainly on the practical elements of the use of stem cells in reproductive medicine, the book also contains a section on new developments in stem cell research. The book is essential reading for reproductive medicine clinicians, gynecologists and embryologists who want to keep abreast of practical developments in this rapidly developing field.