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The timing of cell production by progenitor cells is an essential aspect of development. Particularly during neurogenesis, the time at which neurons and glia are produced affects their function and proper integration into neural circuits. In both the mammalian and Drosophila central nervous system, neural progenitors progressively lose competence to make early-born cell types, so that "old" progenitors can no longer be induced to make "young" neurons. My dissertation work used Drosophila neural progenitors, known as neuroblasts, as a model to investigate the restriction of neural progenitor competence. Drosophila neuroblasts sequentially express temporal transcription factors (TTFs) that determine neural and glial cell fate based on birth-order. For example, the second TTF in the series, Kruppel, is necessary and sufficient for all second-born / third-born fates, regardless of cell type or neuroblast lineage. However, neuroblasts lose competence to respond to Kruppel with each division, ultimately completely losing competence to produce Kruppel-specified cell types at late stages of development. I discovered that chromatin remodeling complexes of the Polycomb group are necessary and sufficient for the temporal restriction of neuroblast competence. I found that Polycomb complexes establish distinct competence windows in neuroblasts that transition from early motorneuron production to late interneuron production. This work provides a mechanistic basis for the restriction of neuroblast competence and supports a model in which Polycomb complexes progressively limit the ability of TTFs to activate gene expression programs that induce early-born fates
The regulation of gene expression in many biological processes involves epigenetic mechanisms. In this new volume, 24 chapters written by experts in the field discuss epigenetic effects from many perspectives. There are chapters on the basic molecular mechanisms underpinning epigenetic regulation, discussion of cellular processes that rely on this kind of regulation, and surveys of organisms in which it has been most studied. Thus, there are chapters on histone and DNA methylation, siRNAs and gene silencing; X-chromosome inactivation, dosage compensation and imprinting; and discussion of epigenetics in microbes, plants, insects, and mammals. The last part of the book looks at how epigenetic mechanisms act in cell division and differentiation, and how errors in these pathways contribute to cancer and other human diseases. Also discussed are consequences of epigenetics in attempts to clone animals. This book is a major resource for those working in the field, as well as being a suitable text for advanced undergraduate and graduate courses on gene regulation.
This book focuses on the intersection between cell cycle regulation and embryo development. Specific modifications of the canonical cell cycle occur throughout the whole period of development and are adapted to fulfil functions coded by the developmental program. Deciphering these adaptations is essential to comprehending how living organisms develop. The aim of this book is to review the best-known modifications and adaptations of the cell cycle during development. The first chapters cover the general problems of how the cell cycle evolves, while consecutive chapters guide readers through the plethora of such phenomena. The book closes with a description of specific changes in the cell cycle of neurons in the senescent human brain. Taken together, the chapters present a panorama of species - from worms to humans - and of developmental stages - from unfertilized oocyte to aged adult.
Nuclear Architecture and Dynamics provides a definitive resource for (bio)physicists and molecular and cellular biologists whose research involves an understanding of the organization of the genome and the mechanisms of its proper reading, maintenance, and replication by the cell. This book brings together the biochemical and physical characteristics of genome organization, providing a relevant framework in which to interpret the control of gene expression and cell differentiation. It includes work from a group of international experts, including biologists, physicists, mathematicians, and bioinformaticians who have come together for a comprehensive presentation of the current developments in the nuclear dynamics and architecture field. The book provides the uninitiated with an entry point to a highly dynamic, but complex issue, and the expert with an opportunity to have a fresh look at the viewpoints advocated by researchers from different disciplines. - Highlights the link between the (bio)chemistry and the (bio)physics of chromatin - Deciphers the complex interplay between numerous biochemical factors at task in the nucleus and the physical state of chromatin - Provides a collective view of the field by a large, diverse group of authors with both physics and biology backgrounds
This volume provides a series of review articles that capture the advances in using the fruit fly, Drosophila melanogaster, model system to address a wide range of cancer-related topics. Articles in this book provide case studies that shed light on the intricate cellular and molecular mechanisms underlying tumor formation and progression. Readers will discover the beauty of the fly model’s genetic simplicity and the vast arsenal of powerful genetic tools enabling its efficient and adaptable use. This model organism has provided a unique opportunity to address questions regarding cancer initiation and development that would be extremely challenging in other model systems. This book provides a useful resource for a researcher who wishes to learn about and apply the Drosophila model to tackle fundamental questions in cancer biology, and to find new ways to fight against this devastating disease.
This indispensable volume highlights recent studies identifying epigenetic mechanisms as essential regulators of skin development, stem cell activity and regeneration. Chapters are contributed by leading experts and promote the skin as an accessible model system for studying mechanisms that control organ development and regeneration. The timely discussions contained throughout are of broad relevance to other areas of biology and medicine and can help inform the development of novel therapeutics for skin disorders as well as new approaches to skin regeneration that target the epigenome. Part of the highly successful Stem Cells and Regenerative Medicine series, Epigenetic Regulation of Skin Development and Regeneration uncovers the fundamental significance of epigenetic mechanisms in skin development and regeneration, and emphasizes the development of new therapies for a number of skin disorders, such as pathological conditions of epidermal differentiation, pigmentation and carcinogenesis. At least six categories of researchers will find this book essential, including stem cell, developmental, hair follicle or molecular biologists, and gerontologists or clinical dermatologists.
Edited and authored by a wealth of international experts in neuroscience and related disciplines, this key new resource aims to offer medical students and graduate researchers around the world a comprehensive introduction and overview of modern neuroscience. Neuroscience research is certain to prove a vital element in combating mental illness in its various incarnations, a strategic battleground in the future of medicine, as the prevalence of mental disorders is becoming better understood each year. Hundreds of millions of people worldwide are affected by mental, behavioral, neurological and substance use disorders. The World Health Organization estimated in 2002 that 154 million people globally suffer from depression and 25 million people from schizophrenia; 91 million people are affected by alcohol use disorders and 15 million by drug use disorders. A more recent WHO report shows that 50 million people suffer from epilepsy and 24 million from Alzheimer’s and other dementias. Because neuroscience takes the etiology of disease—the complex interplay between biological, psychological, and sociocultural factors—as its object of inquiry, it is increasingly valuable in understanding an array of medical conditions. A recent report by the United States’ Surgeon General cites several such diseases: schizophrenia, bipolar disorder, early-onset depression, autism, attention deficit/ hyperactivity disorder, anorexia nervosa, and panic disorder, among many others. Not only is this volume a boon to those wishing to understand the future of neuroscience, it also aims to encourage the initiation of neuroscience programs in developing countries, featuring as it does an appendix full of advice on how to develop such programs. With broad coverage of both basic science and clinical issues, comprising around 150 chapters from a diversity of international authors and including complementary video components, Neuroscience in the 21st Century in its second edition serves as a comprehensive resource to students and researchers alike.
Growing evidence suggests that epigenetic mechanisms play a central role in stem cell biology and are vital for determining gene expression during cellular differentiation and governing mammalian development. In Stem Cell Epigenetics, leading international researchers examine how chromatin regulation and bona fide epigenetic mechanisms underlie stem cell renewal and differentiation. Authors also explore how the diversity of cell types, including the extent revealed by single cell omic approaches, is achieved, and how such processes may be reversed or managed via epigenetic reprogramming. Topics discussed include chromatin in pluripotency, stem cells and DNA methylation, histone modifications in stem cells and differentiation, higher-order chromatin conformation in pluripotent cells, stem cells and cancer, epigenetics and disease modeling, brain organoids from pluripotent cells, transcriptional regulation in stem cells and differentiation, non-coding RNAs in pluripotency and early differentiation, and diseases caused by epigenetic alterations in stem cells. Additionally, the book discusses the potential implementation of stem cell epigenetics in drug discovery, regenerative medicine, and disease treatment. Stem Cell Epigenetics will provide researchers and physicians with a state-of-the-art map to orient across the frontiers of this fast-evolving field. Analyzes the role of epigenetics in embryonic stem cell regulation Indicates the epigenetic mechanisms involved in stem cell differentiation and highlights modifications and misregulations that may result in disease pathogenesis Examines the potential applications of stem cell epigenetics in therapeutic disease interventions and regenerative medicine, providing a foundation for researchers and physicians to bring this exciting and fast-evolving field into a clinical setting Features chapter contributions by leading international experts
This second edition provides updated and new chapters on selected genetic, molecular, biochemical, and cell biological techniques. Chapter’s guide readers through methods and principles on primordial germ cells and germline stem cells, however many of these principles can be applied to different types of adult stem cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Germline Stem Cells: Second Edition aims to present the new findings and techniques that have developed since the first edition.
Stem cells have been gaining a lot of attention in recent years. Their unique potential to self-renew and differentiate has turned them into an attractive model for the study of basic biological questions such as cell division, replication, transcription, cell fate decisions, and more. With embryonic stem (ES) cells that can generate each cell type in the mammalian body and adult stem cells that are able to give rise to the cells within a given lineage, basic questions at different developmental stages can be addressed. Importantly, both adult and embryonic stem cells provide an excellent tool for cell therapy, making stem cell research ever more pertinent to regenerative medicine. As the title The Cell Biology of Stem Cells suggests, our book deals with multiple aspects of stem cell biology, ranging from their basic molecular characteristics to the in vivo stem cell trafficking of adult stem cells and the adult stem-cell niche, and ends with a visit to regeneration and cell fate reprogramming. In the first chapter, “Early embryonic cell fate decisions in the mouse”, Amy Ralson and Yojiro Yamanaka describe the mechanisms that support early developmental decisions in the mouse pre-implantation embryo and the current understanding of the source of the most immature stem cell types, which includes ES cells, trophoblast stem (TS) cells and extraembryonic endoderm stem (XEN) cells.