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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.
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.
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.
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.
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 open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
" . . . but our knowledge is so weak that no philosoph er will ever be able to completely explore the nature of even a fly . . . " * Thornas Aquinas "In Syrnbolurn Apostolorum" 079 RSV p/96 This is a monograph on embryogenesis of the fruit fly Drosophi la melanogaster conceived as a reference book on morphology of embryonie development. A monograph of this extent and con tent is not yet available in the literature of Drosophila embryolo gy, and we believe that there is areal need for it. Thanks to the progress achieved during the last ten years in the fields of devel opmental and molecular genetics, work on Drosophila develop ment has considerably expanded creating an even greater need for the information that we present here. Our own interest for wildtype embryonie development arose several years ago, when we began to study the development of mutants. While those studies were going on we repeatedly had occasion to state in sufficiencies in the existing literature about the embryology of the wildtype, so that we undertook investigating many of these problems by ourselves. Convinced that several of our colleagues will have encountered similar difficulties we decided to publish the present monograph. Although not expressely recorded, Thomas Aquinas probably referred to the domestic fly and not to the fruit fly. Irrespective of which fly he meant, however, we know that Thomas was right in any case.