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The establishment of polarity is a fundamental process of neural development at multiple levels from synaptogenesis to building up neural circuits. At the circuit level, extrinsic cues, serving as attractive or repulsive signals, guide the pathfinding of axons, regulate the morphogenesis of dendritic arbors, and mediate synapse formation between specific pre- and postsynaptic partners at particular loci. Within a neuron, on the other hand, intrinsic mechanisms instruct the proper polarized subcellular distribution of microtubules, synaptic vesicles, neurotransmitter receptors and channels, etc. The establishments of polarized structures at both levels together ensure the unidirectional signal transmission in the complex neural network and orderly functional nervous system. The nematode Caenorhabditis elegans, with only 302 neurons whose cell fates, developmental processes and wiring partners well-identified, provides us with a good model organism to understand how polarized structures are built up at both the circuit and cellular levels. At the circuit level, we investigated the synaptic specificity in the C. elegans egg-laying circuit, where presynaptic neurons select one type of muscles, the vm2, as targets and form synapses on the dendritic spine-like muscle arms. Using forward genetic approaches, we found that the Notch-Delta signaling pathway was required to distinguish the target and non-target muscles. APX-1/Delta acts in the surrounding tissues, including the non-target muscle vm1, to activate LIN-12/Notch in the target muscle vm2. LIN-12 cell-autonomously promotes the expression of UNC-40/DCC and MADD-2 in vm2 for muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in the non-target vm1 is sufficient to induce the polarized extension of muscle arms from the non-target vm1. Therefore, intercellular signaling via LIN-12/Notch instructs the formation of dendritic spine-like muscle arms and the specific postsynaptic target selection. We also investigated the polarity establishment at the subcellular level. In particular, we asked how intrinsic sorting machineries separate axonal and dendritic proteins, target them to their specific domains, and achieve polarized protein distributions in the axon and the dendrite. We identified compartment specific di-leucine motifs that are necessary and sufficient to target proteins to either the axon or the dendrite. We showed that the axonal di-leucine motifs are recognized by AP-3, a clathrin-associated adaptor protein (AP) complex. In contrast, dendritic di-leucine motifs are recognized by a different AP, named AP-1. Using both genetics and biochemical approaches, we found that the axonal di-leucine motifs bind to AP-3 with higher affinity than to AP-1, which underlies the sorting specificity. We also showed that axonal and dendritic proteins are packaged and transported on different cargo vesicles derived from the trans-Golgi network (TGN). AP-3 and AP-1 complexes are selectively required for forming the axonal and dendritic vesicles from the TGN, respectively. Thus, the AP-3 and AP-1 dependent sorting machineries instruct the properly polarized distributions of axonal and dendritic cargoes, support the efficient neurotransmission, and ensure normal neuronal activity. In summary, we explored mechanisms for building up the polarized structures at both the circuit level and subcellular levels of the nervous system. Extrinsic and intrinsic cues both contribute to the establishment of neural polarity, which in turn forms the fundamental basis of neural function.
Comprehensive Overview of Advances in OlfactionThe common belief is that human smell perception is much reduced compared with other mammals, so that whatever abilities are uncovered and investigated in animal research would have little significance for humans. However, new evidence from a variety of sources indicates this traditional view is likely
Derived from the acclaimed online “WormAtlas,†C. elegansAtlas is a large-format, full-color atlas of the hermaphroditic form of the model organism C. elegans, known affectionately as “the worm†by workers in the field. Prepared by the editors of the WormAtlas Consortium, David H. Hall and Zeynep F. Altun, this book combines explanatory text with copious, labeled, color illustrations and electron micrographs of the major body systems of C. elegans. Also included are electron microscopy cross sections of the worm. This laboratory reference is essential for the working worm biologist, at the bench and at the microscope, and provides a superb companion to the C. elegansII monograph. It is also a valuable tool for investigators in the fields of developmental biology, neurobiology, reproductive biology, gene expression, and molecular biology.
Intracellular cell signaling is a well understood process. However, extracellular signals such as hormones, adipokines, cytokines and neurotransmitters are just as important but have been largely ignored in other works. Aimed at medical professionals and pharmaceutical specialists, this book integrates extracellular and intracellular signalling processes and offers a fresh perspective on new drug targets.
Defines the current status of research in the genetics, anatomy, and development of the nematode C. elegans, providing a detailed molecular explanation of how development is regulated and how the nervous system specifies varied aspects of behavior. Contains sections on the genome, development, neural networks and behavior, and life history and evolution. Appendices offer genetic nomenclature, a list of laboratory strain and allele designations, skeleton genetic maps, a list of characterized genes, a table of neurotransmitter assignments for specific neurons, and information on codon usage. Includes bandw photos. For researchers in worm studies, as well as the wider community of researchers in cell and molecular biology. Annotation copyrighted by Book News, Inc., Portland, OR
The book provides an overview on the different aspects of gene regulation from an mRNA centric viewpoint, including how mRNA is assembled and self-assembles in a complex consisting of RNA and proteins, and how its ability to be translated at the right time and space depends on many processes acting on the mRNAs, leading to a properly folded complex. This book shows how new technologies have led to a better understanding of these processes and their connected diseases.The book is written for scientists in fundamental and applied biomedical research working on different aspects of gene regulation. It is also targeted to an audience that is not implicated in these fields directly, but wants to gain a better understanding of mRNA biology.
This monograph explores the relationships between cell signaling and the cytoplasmic cytoskeleton in fundamental cell processes, thus bridging the gap between two very active aspects of molecular cell biology. It covers the two main - and reciprocal - questions of these relationships: How are structure and function of the cytoskeleton affected by external signals which impinge on the cell? How does the cytoskeleton influence the cellular signaling processes which determine cell behavior?