Molecular Mechanisms Of Neural Development And Insights Into Disease

Neural Development and Disease, Volume 142 in the Current Topics in Developmental Biology series highlights new advances in the field, with this new volume presenting interesting chapters by one or more members of an international board of authors. Sections in this new release cover The role of primary cilia in neural development and disease, Mechanisms of axon guidance receptor regulation and signaling, Synaptic recognition molecules in development and disease, The regulation of cortical neurogenesis, Axon guidance in the developing spinal cord, The role of astrocytes in synapse formation and maturation, Development of motor circuits, Molecular mechanisms that mediate dendrite morphogenesis, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Current Topics in Developmental Biology series

With the unprecedented identification of new mutation mechanisms in neurodegenerative diseases and the emergence of common mechanisms among diseases that were once considered unrelated, neurobiologists are poised for the development of new therapies based on high throughput screenings and a better understanding of the molecular and cellular mechanisms leading to neurodegeneration. In Molecular Mechanisms of Neurodegenerative Diseases, Marie-Francoise Chesselet, MD, PhD, and a panel of leading researchers and neurologists from industry and academia critically review the most recent advances from different yet complementary points of view. Focusing on Alzheimer's, Parkinson's, and CAG triplet repeat diseases, the authors show how studies of cellular and genetically engineered animal models have enhanced our understanding of the molecular mechanisms of neurodegenerative diseases and may lead to the development of new therapeutics. Topics include the role of Ab toxicity, glial cells, and inflammation in Alzheimer's disease; the formation of abnormal protein fragments across several diseases, the impact of dopamine and mitochondrial dysfunction on neurodegeneration; and the potential of genetics to identify the molecular mechanisms of neurodegenerative diseases. Authoritative and insightful, Molecular Mechanisms of Neurodegenerative Diseases synthesizes the novel ideas and concepts now emerging to create a fresh understanding of neurodegenerative disorders, one that promises to lead to powerful new therapies that prevent, delay the onset, slow the progression, or even cure these cruel diseases.

The last decades have witnessed a radical change in our views on central nervous system damage and repair. This change is not only due to the emergence of new powerful tools for the analysis of the brain and its reactions to insults, but it also reflects a conceptual change in the way we approach these problems. As an illustration to this development, it is instructive to go back to the proceedings of a meeting at the NIH in 1955 edited by William F. Windle, which summarizes the disillusioned and pessimistic view on CNS regeneration prevailing at the time. While this generation of researchers were well aware of the issues at stake, they felt they had reached the end of the road; the approaches they had pursued had got stuck and the tools available could not take them any further. I can very well imagine that the participants, most of them leaders in the field, left that conference feeling they had heard their field being sentenced to death.

Comprehensive, up-to-date and authoritative, this volume covers all the recent advances in understanding the early events of neural development at the molecular and cellular levels. The authors detail the applications of molecular genetic methods to the study of neural induction, neuronal phenotypes and processes, and the formation of specific patterns of connections. They analyze the new information generated through modern techniques for identifying, cloning, deleting and introducing specific genes, for labeling neuronal or glial precursors, and for imaging individual neurons or parts of neurons. Other chapters focus on the increasing use of a variety of model organisms: fruit flies, nematode worms, zebra fish, xenopus frogs, chicks, and mice. The improved conservation of DNA and protein sequences, and the availability of gene and protein databases have made it possible to rapidly identify gene homologues in organisms sometimes separated by hundreds of millions of years of evolution. This volume features several chapters co-authored by investigators one of whom works on vertebrates and the other on invertebrates. They demonstrate clearly that although the nervous systems of a fruit fly and a mouse, for example, are quite different in appearance and organization, many of the same molecular players and cellular processes are involved in their assembly. Molecular and Cellular Approaches to Neural Development will be of great practical interest to researchers, graduate students and post-doctoral fellows in developmental, cell and molecular biology, genetics, and neuroscience.

This volume addresses central issues in the embryological development of the nervous system, which, while similar to that of other organs and tissues, features special and intricate mechanisms of morphogenesis. It emphasizes the description of cellular interactions at the molecular level and includes some of the first fruits from applications to neurobiology of recent developments in othera areas--notable immunology, biochemistry, molecular biology, and molecular genetics.

The brain consists of a complex but precisely organized neural network, which provides the structural basis of higher order functions. Such a complex structure originates from a simple pseudostratified neuroepithelium. During the developing mammalian cerebral cortex, a cohort of neural progenitors, located near the ventricle, differentiates into neurons and exhibits multi-step modes of migration toward the pial surface. Tight regulation of neurogenesis and neuronal migration is essential for the determination of the neuron number in adult brains and the proper positioning of excitatory and inhibitory neurons in a specific layer, respectively. In addition, defects in neurogenesis and neuronal migration can cause several neurological disorders, such as microcephaly, periventricular heterotopia and lissencephaly. Recent advances in genetic approaches to study the developing cerebral cortex, as well as the use of a number of novel techniques, particularly in vivo electroporation and time-lapse analyses using explant slice cultures, have significantly increased our understanding of cortical development. These novel techniques have allowed for cell biological analyses of cerebral cortical development in vivo or ex vivo, showing that many cellular events, including endocytosis, cell adhesion, microtubule and actin cytoskeletal regulation, neurotransmitter release, stress response, the consequence of cellular crowding (physical force), dynamics of transcription factors, midbody release and polarity transition are required for neurogenesis and/or neuronal migration. The aim of this research topic is to highlight molecular and cellular mechanisms underlying cerebral cortical development and its related neurological disorders from the cell biological point of views, such as cell division, cell-cycle regulation, cytoskeletal organization, cell adhesion and membrane trafficking. The topic has been organized into three chapters: 1) neurogenesis and cell fate determination, 2) neuronal migration and 3) cortical development-related neurological disorders. We hope that the results and discussions contributed by all authors in this research topic will be broadly useful for further advances in basic research, as well as improvements in the etiology and care of patients suffering from neurological and psychiatric disorders.

The nervous system is highly complex both in its structural order and in its ability to perform the many functions required for survival and interaction with the environment; understanding how it develops has proven to be one of the greatest challenges in biology. Such precision demands that key events at every developmental stage are executed properly and are coordinated to produce the circuitry underlying each of the adult nervous system's functions. This volume describes the latest research on the cellular and molecular mechanisms of neural circuitry development, while providing researchers with a one-stop overview and synthesis of contemporary thought in the area. Reviews current research findings on the development of neural circuitry, providing researchers with an overview and synthesis of the latest contemporary thought in the cellular and molecular mechanisms that underlie the development of neural circuitry Includes chapters discussing topics such as the guidance of nerve growth and the formation of plasticity of synapses, helping researchers better understand underlying mechanisms of neural circuit development and maintenance that may play a role in such human diseases/conditions as depression, anxiety, and pain Chapters make use of a variety of human and animal models, allowing researchers to compare and contrast neural circuitry development across a wide spectrum of models

Cell-Cycle Mechanisms and Neuronal Cell Death examines the role of cell cycle activation in the molecular mechanisms leading to neuronal degeneration. Leading Authors discuss this topic in relation to the major neurological disorders, including Alzheimer’s disease, stroke and epilepsy. This book serves to gain new insights into the molecular determinants of neuronal death and to establish new targets for therapeutic intervention.

New advances in understanding the generation of cell diversity in the developing vertebrate nervous system are presented, bringing together different perspectives and approaches as well as the use of different biological systems under a general theme. As a result, the reader is able to draw from a vast resource of information. In addition to studies on development, some articles concentrate on disease and allow direct comparison of the molecular mechanisms implicated in both development and disease. Developmental neuroscientists who are interested in neural cell fate determination as well as people working in areas of neural disease such as multiple sclerosis will profit most from this issue.