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Nervous system function, from sensory perception to motor control and cognition, requires the correct wiring of neural circuits during development. The establishment of these circuits consists of the growth and guidance of signal-sending axons and signal-receiving dendrites to their correct targets. Despite being exposed to the same molecular environment, a neuron's axon and dendrites have different morphologies and targets. Using the C. elegans DA9 motoneuron we explore mechanisms of dendrite growth and how a dendrite-specific response is achieved to a cue regulating axons and dendrites. We found that DA9 dendrite development is spatially and temporally distinct from the axon. While the axon grows embryonically, the dendrite develops postembryonically. Characterizing DA9 dendrite growth in larvae, adults and body size mutants suggests that it is not driven by size, but rather by a local cue. A candidate approach to identify this cue taught us that the guidance cue UNC-6/Netrin is required for both axon and dendrite development in DA9. The UNC-6 repulsive receptor UNC-5 repels the axon from the ventral nerve cord, while the attractive receptor UNC-40 is dendritically enriched and promotes antero-posterior dendrite growth. While ventrally secreted UNC-6 instructs axon guidance, dorsal or even membrane-tethered UNC-6 can support dendrite development. Surprisingly, the kinase PAR-4/LKB1 is selectively required for UNC-40 signaling in dendrite outgrowth. Finally, we found that the C-terminal motor kinesin KLP-16 also promotes DA9 dendrite growth and that its enrichment at the DA9 dendrite distal tip may be partially regulated by PAR-4/LKB1. These data suggest that axon and dendrite of one neuron interpret common environmental cues with different receptors and downstream signaling pathways.
The first of its kind, this laboratory handbook emphasizes diverse methods and technologies needed to investigate C. elegans, both as an integrated organism and as a model system for research inquiries in cell, developmental, and molecular biology, as well as in genetics and pharmacology. Four primary sections--Genetic and Culture Methods, Neurobiology, Cell and Molecular Biology, and Genomics and Informatics--reflect the cross-disciplinary nature of C. elegans research. Because C. elegans is a simple and malleable organism with a small genome and few cell types, it provides an elegant demonstr.
This book gives an overview of various interactomes involved in dorsal ventral (DV) and anterior posterior (AP) guidance, their mechanisms of action, subcellular localizations, and functional roles. It will provide readers a better understanding of the development of the nervous system, which in turn will help to find cures to various neural and other disorders.​ In nematodes there are two types of guidance systems, including DV and AP guidance. The signaling process that guides the growth cones along the DV axis has remained intact in both vertebrates and invertebrates. The adaptor protein UNC-53 appears to play a part in migration along the AP axis in both worms and their human homologs. “Neuron Navigators” (NAV) are also involved in nervous system development ​
Since the discovery of actin by Straub in the 1950’s and the pioneering work of Oosawa on actin self-assembly in helical laments in the 1960’s, many books and conference proceedings have been published. As one of the most essential p- teins in life, essential for movement in organisms rangingfrom bacteria to higher eukaryotes, it is no surprise that actin has fascinated generations of scientists from many different elds. Actin can be considered as a “living treasure” of biology; the kinetics and thermodynamics of self-assembly, the dissipative nature of actin po- merization, the molecular interactions of monomeric and polymerized actin with regulators, the mechanical properties of actin gels, and more recently the force p- ducing motile and morphogenetic processes organized by the actin nanomachine in response to signaling, are all milestones in actin research. Discoveries that directly derive from and provide deeper insight into the fundamental properties of actin are constantly being made, making actin an ever appealing research molecule. At the same time, the explosion in new technologies and techniques in biological sciences has served to attract researchers from an expanding number of disciplines, to study actin. This book presents the latest developments of these new multiscale approaches of force and movement powered by self-assembly processes, with the hope to opening our perspectives on the many areas of actin-based motility research.
Intracellular Signalling Proteins, Volume 116, presents an overview of the current developments in mechanisms of intracellular signaling and involvement of these mechanisms in the development of a number of disorders and diseases. Opportunities for targeting the intracellular signaling cascades for benefiting patients are also discussed, along with chapters that focus on Voices from the Dead: The Complex Language of Dead Cells, Nucleobindins and Encoded Peptides: From Cell Signalling to Physiology, Estrogen Receptor Signaling Mechanisms, Intracellular Signaling of the AMP-Activating Protein Kinase, the Relationship between Mitofusin 2 and Cancer, Molecular Signaling in Bone Cells: Regulation Cell Differentiation and Survival, and more. - Describes advances in the discovery and application of therapeutics that target intracellular signaling mechanisms - Targeted to a very wide audience of specialists, researchers and students - Contains timely chapters written by well-renowned authorities in their field - Includes a number of high quality illustrations, figures and tables
This book, which was written by the current leaders in the field of Ras research, provides the readers with the most comprehensive and up-to-date view of the major oncogene Ras. This volume is valuable not only for university students in molecular biology, biochemistry or medicine, but also for senior scientists currently conducting cancer research.
Nutraceuticals: Efficacy, Safety and Toxicity, Second Edition, brings together everything that is currently known about nutraceuticals and their potential toxic effects. The book introduces readers to nutraceuticals, herbal medicines, Ayurvedic medicines, prebiotics, probiotics, adaptogens, and their uses and specific applications. This essential reference discusses the mechanism of action for the judicious use of these nutraceuticals and the best tools for their evaluation before detailing the safety and toxicity of nutraceuticals and interactions with other therapeutic drugs. Finally, and crucially, regulatory aspects from around the world are covered. Completely revised and updated, this updated edition provides toxicologists, pharmacologists, pharmaceutical scientists, and those interested in medicinal plants and natural products with a comprehensive overview of the most effective tools upon which to evaluate the safety and toxicity of nutraceuticals, prebiotics, probiotics and alternative medicines. - Presents a completely revised and updated resource on the impact of nutraceuticals and various disease states such as diabetes and ophthalmic and dermal diseases - Grants an overview of the current state-of-the-science of nutraceuticals, their use and applications, and known adverse effects - Provides effective tools to evaluate the potential toxicity of any nutraceutical - Includes details of regulatory issues as written by international experts
Patterning and Cell Type Specification in the Developing CNS and PNS, Second Edition, the latest release in the Comprehensive Developmental Neuroscience series, presents recent advances in genetic, molecular and cellular methods that have generated a massive increase in new information. The book provides a much-needed update to underscore the latest research in this rapidly evolving field, with new section editors discussing the technological advances that are enabling the pursuit of new research on brain development. This volume focuses on neural patterning and cell type specification in the developing central and peripheral nervous systems. - Features leading experts in various subfields as section editors and article authors - Contains articles that are peer reviewed to ensure accuracy, thoroughness and scholarship - Covers mechanisms which control regional specification, regulate proliferation of neuronal progenitors, control differentiation and survival of specific neuronal subtypes, and control the development of non-neural cells