Molecular Mechanisms of Axon Guidance in the Developing Spinal Cord

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ISBN 13 : 9781109352573
Total Pages : 124 pages
Book Rating : 4.3/5 (525 download)

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Book Synopsis Molecular Mechanisms of Axon Guidance in the Developing Spinal Cord by : Liseth M. Parra

Download or read book Molecular Mechanisms of Axon Guidance in the Developing Spinal Cord written by Liseth M. Parra and published by . This book was released on 2009 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: The formation of intricate neural circuits requires that nascent axons navigate the complex environment of the developing embryo and precisely determine the trajectories that would lead them to their final synaptic targets. Although many guidance cues and their receptors have been identified, the intracellular signaling cascades that control and direct axonal growth remained to be fully understood. Developing axons constantly reassess the immediate environment to distinguish between a myriad of guidance molecules that are simultaneously present along their trajectory. Exactly how the axon interpret these signals at a specific time and space are limited, thus understanding how guidance cues work in concert during axonal pathfinding is a major goal in developmental neurobiology and in the regeneration of axonal connections after injury and disease. In this dissertation we studied the pathfinding of spinal cord commissural axons to understand the molecular mechanisms underlying changes in axonal responses from attraction to repulsion during floor plate crossing at the spinal cord ventral midline. Here, we found that chemorepellent signals emanating from floor plate cells of the Slit and class 3 Semaphorin family of proteins synergize in vitro to repel precrossing commissural axons possibly through Neuropilin2 pathways. In addition, we propose that Sonic Hedgehog (Shh) plays a pivotal role in mediating commissural axon repulsive guidance during floor plate crossing. We provide evidence that Shh is a regulator of class 3 Semaphorin signals in precrossing axons and specifically show that knockdown of Shh pathway components, Patched1 (PTC1) and Smoothened (Smo) disrupted proper guidance of commissural axons during floor plate crossing. We also show that both Smo and PTC1 are expressed around the developmental stages we studied and are key determinants of this regulation. The third major finding of this dissertation is that the activation of Semaphorin3 signals by Shh might be induced through the alteration of cAMP/PKA levels via Smo dependent activation of inhibitory G alpha proteins. Together the data presented in this dissertation propose new exciting models in which axon guidance regulatory pathways can induce profound changes in axonal navigational responses by successfully integrating and interpreting signaling inputs from external and internal axon guidance systems.

Molecular and Mechanisms that Guide Axons in the Developing Vertebrate Spinal Cord

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ISBN 13 :
Total Pages : 750 pages
Book Rating : 4.:/5 (82 download)

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Book Synopsis Molecular and Mechanisms that Guide Axons in the Developing Vertebrate Spinal Cord by : Katja Brose

Download or read book Molecular and Mechanisms that Guide Axons in the Developing Vertebrate Spinal Cord written by Katja Brose and published by . This book was released on 2000 with total page 750 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Molecular Mechanisms of Neural Development and Insights into Disease

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Publisher : Academic Press
ISBN 13 : 0128152826
Total Pages : 546 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Molecular Mechanisms of Neural Development and Insights into Disease by :

Download or read book Molecular Mechanisms of Neural Development and Insights into Disease written by and published by Academic Press. This book was released on 2021-03-09 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Molecular Mechanisms Orchestrating Commissural Axon Guidance

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ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (123 download)

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Book Synopsis Molecular Mechanisms Orchestrating Commissural Axon Guidance by : Sergi Roig Puiggros

Download or read book Molecular Mechanisms Orchestrating Commissural Axon Guidance written by Sergi Roig Puiggros and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Commissural neurons ensure the coordination of motor and somatosensory information between halves of the central nervous system. In the caudal part of the CNS, commissural axons, first grow toward the ventral midline, the floor plate, to cross it and reach their final target. The cellular and molecular mechanisms controlling midline crossing have been extensively studied. Ram--n y Cajal, in his neurotropic theory, suggested that floor plate cells could release diffusible factors chemo-attracting commissural axons to the ventral midline. Netrin-1, a protein discovered more than 2 decades ago, is a secreted protein expressed both by floor plate cells and ventricular zone progenitors and with long-range chemoattractive activity in vitro. Today, Netrin-1 is widely accepted as the textbook example of long-range chemoattractive guidance cue. However, our results, challenge this model by proposing a short-range mechanism of action for Netrin-1 during commissural axon guidance. Indeed, we determined that floor plate-derived netrin-1 is dispensable for commissural axon guidance. Instead, ventricular zone-derived netrin-1 is necessary and sufficient to promote the dorso-ventral extension of hindbrain commissural axons and midline crossing. We also confirmed that ventricular zone progenitors are the main Netrin-1 source for ventrally migrating precerebellar neurons. In addition, we observe that in absence of ventricular zone-derived netrin-1, commissural axons and precerebellar neurons cell bodies invade several cranial nerves. This appears to be a cell- autonomous and Dcc-dependent process. This mechanism is not conserved in the spinal cord, where both netrin-1 sources act synergistically to ensure commissural axon guidance and midline crossing. Commissural neurons are diverse and found throughout the nervous system. To analyse the molecular diversity of hindbrain and spinal cord commissural neurons, we used approaches combining mouse genetics and transcriptomics. We are currently working on some novel transcription factors that might play a role in the development of hindbrain and spinal cord commissural neurons.

Planar Cell Polarity Pathway and Axon Guidance in the Developing Spinal Cord

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ISBN 13 : 9781109686753
Total Pages : 105 pages
Book Rating : 4.6/5 (867 download)

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Book Synopsis Planar Cell Polarity Pathway and Axon Guidance in the Developing Spinal Cord by : Jeong Deok Beth Shafer

Download or read book Planar Cell Polarity Pathway and Axon Guidance in the Developing Spinal Cord written by Jeong Deok Beth Shafer and published by . This book was released on 2010 with total page 105 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ability of the mammalian central nervous system to interpret the environment accurately, integrate information efficiently, and generate appropriate responses depends on the precise wiring and organization of billions of neurons into functional networks. The establishment of neural circuits to enable the eventual flow of sensory information requires that axons navigate across vast (on a cellular scale) distances. For somatosensory neurons, guidance takes place during development when axons must grow to the brain via a series of intermediate targets, each step of which involves the detection and response to numerous extracellular cues. Therefore, to develop a comprehensive understanding of how neurons form appropriate connections requires that axonal responses to these molecular guidance cues be clearly defined. This dissertation presents studies of axon guidance in a model cellular system, the somatosensory commissural neurons of the spinal cord. I have characterized the role of Wnt-Frizzled signaling in these neurons, and found that the non-canonical Wnt-Fzd signaling, known as the Planar Cell Polarity (PCP) pathway, is fundamental to commissural axon guidance. Further, by analysis of animal models of PCP dysfunction, Celsr3 null and Vangl2 mutant mice, I show that PCP is required for anterior guidance of commissural axons toward the brain. Equally important, I describe the mechanism by which the PCP pathway mediates axon growth decisions through the use of primary spinal neuron and eukaryotic cell cultures and biochemical techniques. I present evidence to show that modifications of PCP surface receptors, Fzd3 and Vangl2, at the cell membrane are critical to PCP signaling and constitute a spatio-temporal response to Wnt molecules secreted from the ventral spinal cord. Together, these data reveal a novel role for the PCP pathway in axon guidance. It is hoped that the results of these studies will provide a more general model for the role of membrane receptor modifications in the establishment of neuronal circuitry.

Axon Growth and Guidance

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Publisher : Springer Science & Business Media
ISBN 13 : 0387767150
Total Pages : 184 pages
Book Rating : 4.3/5 (877 download)

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Book Synopsis Axon Growth and Guidance by : Dominique Bagnard

Download or read book Axon Growth and Guidance written by Dominique Bagnard and published by Springer Science & Business Media. This book was released on 2008-12-10 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book proposes an updated view of the current knowledge of the molecular and cellular mechanisms ensuring axon growth and guidance. The introductory chapter will remind the readers of all the features of a growth cone and the mechanisms controlling its growth. From there, one enters a fabulous journey with a growth cone, a Tom Thumb story filled with molecular encounters and complex interactions leading to one of the most fantastic developmental achievements: the nervous system wiring.

Cellular and Molecular Mechanisms of Stereotyped Axon Pruning in the Central Nervous System

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ISBN 13 :
Total Pages : 314 pages
Book Rating : 4.:/5 (85 download)

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Book Synopsis Cellular and Molecular Mechanisms of Stereotyped Axon Pruning in the Central Nervous System by : Lawrence Kong Low

Download or read book Cellular and Molecular Mechanisms of Stereotyped Axon Pruning in the Central Nervous System written by Lawrence Kong Low and published by . This book was released on 2008 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Molecular Mechanisms Underlying the Response of Commissural Axons to Netrin-1

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ISBN 13 :
Total Pages : 446 pages
Book Rating : 4.:/5 (66 download)

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Book Synopsis Molecular Mechanisms Underlying the Response of Commissural Axons to Netrin-1 by : Christine Mirzayan

Download or read book Molecular Mechanisms Underlying the Response of Commissural Axons to Netrin-1 written by Christine Mirzayan and published by . This book was released on 1997 with total page 446 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Cellular Migration and Formation of Neuronal Connections

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Publisher : Academic Press
ISBN 13 : 0123973473
Total Pages : 1081 pages
Book Rating : 4.1/5 (239 download)

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Book Synopsis Cellular Migration and Formation of Neuronal Connections by :

Download or read book Cellular Migration and Formation of Neuronal Connections written by and published by Academic Press. This book was released on 2013-05-06 with total page 1081 pages. Available in PDF, EPUB and Kindle. Book excerpt: The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development and on new psychiatric/neurological treatments being developed based on our increased understanding of developmental mechanisms. Each volume in the series consists of review style articles that average 15-20pp and feature numerous illustrations and full references. Volume 2 offers 56 high level articles devoted mainly to Formation of Axons and Dendrites, Migration, Synaptogenesis, Developmental Sequences in the Maturation of Intrinsic and Synapse Driven Patterns. Series offers 144 articles for 2904 full color pages addressing ways in which the nervous system and its components develop Features leading experts in various subfields as Section Editors and article Authors All articles peer reviewed by Section Editors to ensure accuracy, thoroughness, and scholarship Volume 2 sections include coverage of mechanisms which regulate: the formation of axons and dendrites, cell migration, synapse formation and maintenance during development, and neural activity, from cell-intrinsic maturation to early correlated patterns of activity

The Role of 14-3-3 Proteins in Spinal Cord Commissural Neuron Axon Guidance and Oligodendrocyte Differentiation

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ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (111 download)

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Book Synopsis The Role of 14-3-3 Proteins in Spinal Cord Commissural Neuron Axon Guidance and Oligodendrocyte Differentiation by : Ricardo Alchini

Download or read book The Role of 14-3-3 Proteins in Spinal Cord Commissural Neuron Axon Guidance and Oligodendrocyte Differentiation written by Ricardo Alchini and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The current work seeks to understand some of the molecular mechanisms that act regulating the development of the central nervous system (CNS). We focus on the role of a family of adaptor proteins called 14-3-3s. The first two chapters are devoted to the field of axon guidance. During development, neurons must project their axons towards appropriate targets in order to establish physiologically relevant connections. To navigate properly they must interpret a complex molecular environment, a role that is fulfilled by the growth cone. Our group has previously identified 14-3-3 proteins, a family of adaptor proteins, as being major constituents of growth cones. Their importance for axonal repulsion has been described linking these proteins to the modulation of repulsion responses via antagonism to the protein kinase A. First, we describe the local ex utero electroporation technique we designed to observe axonal development in organotypic cultures of the spinal cord, and then we offer examples of its use. Next, we present this use of ex utero electroporation as a starting point to study the role of 14-3-3 proteins in the development of the spinal cord circuitry, which is further explained through the investigation of the downstream signaling. We show that 14-3-3 loss of function leads to disorganization of spinal cord commissural fibers ex vivo. This phenotype is attributed to an impairment in responsiveness to Netrin, an important attractant expressed by the floorplate. We implicate 14-3-3 loss of function results in abnormal activation of the small GTPase Rac1. We describe the 14-3-3[zeta] isoform as a key player in this process and demonstrate that a lack 14-3-3[zeta] results in guidance errors of commissural fibers projecting to the floorplate. Finally, we wanted to explore the role of 14-3-3s in different cell types of the CNS. Chapter 3 examines the expression pattern of 14-3-3 proteins in differentiating oligodendrocytes, the myelinating cells of the CNS. We show that most 14-3-3 isoforms are expressed by oligodendrocytes in vitro, and that 14-3-3 loss of function improves their differentiation. Further studies will define the molecular mechanisms involved in this process. Together we describe the importance of 14-3-3 proteins in the guidance of pre-crossing commissural neurons and show that 14-3-3 proteins are potential targets for future remyelination therapies. " --

Mechanisms of Axon Pathfinding and Survival

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ISBN 13 :
Total Pages : 284 pages
Book Rating : 4.:/5 (68 download)

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Book Synopsis Mechanisms of Axon Pathfinding and Survival by : Ali Genie Fenstermaker

Download or read book Mechanisms of Axon Pathfinding and Survival written by Ali Genie Fenstermaker and published by . This book was released on 2010 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development of functional neuronal circuits occurs via a series of complex events including axon pathfinding and synapse formation followed by selective pruning and refining of these circuits by means of programmed cell death and axon degeneration. The precise molecular machinery that dictates these exquisite development events is not well understood. My thesis study examines the role of Wnt signaling throughout nervous system development. Wnts have recently been identified as axon guidance molecules but the signaling pathways that mediate growth cone turning have yet to be elucidated. Furthermore, is there a connection between these guidance events and subsequent developmental pruning? To study the role of Wnt signaling through these events, I employed a variety of techniques including analysis of genetically modified mice, ex utero electroporation of rat spinal cord cultures, and pharmacological and genetic manipulation of dissociated neuronal cultures. Throughout this study, we will demonstrate that indeed, Wnt signaling mediates multiple events critical for appropriate nervous system development including appropriate anterior-posterior axon guidance of both spinal cord commissural neurons and monoaminergic neurons in the brainstem. In addition, I explored the potential role for an axon guidance pathway in mediating neuron survival. Here I investigate the role of atypical PKC (aPKC) signaling in the survival of developing cortical neurons. Inhibition of aPKC resulted in rapid axon fragmentation. We posit that not only does Wnt proteins serve as guidance cues in the developing nervous system, but that these attractive cues might also serve as trophic signals to developing axons.

The Molecular Mechanisms of Anterior-posterior Guidance of Spinal Cord Commissural Axons

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ISBN 13 : 9780549157335
Total Pages : 282 pages
Book Rating : 4.1/5 (573 download)

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Book Synopsis The Molecular Mechanisms of Anterior-posterior Guidance of Spinal Cord Commissural Axons by : Alexander Matthew Wolf

Download or read book The Molecular Mechanisms of Anterior-posterior Guidance of Spinal Cord Commissural Axons written by Alexander Matthew Wolf and published by . This book was released on 2007 with total page 282 pages. Available in PDF, EPUB and Kindle. Book excerpt: Wnt proteins are conserved axon guidance cues that direct growth cone navigation. However, the intracellular signaling mechanisms that lead to changes of cytoskeleton or membrane dynamics involved in growth cone turning are unknown. We previously showed that Wnt-Frizzled signaling directs spinal cord commissural axons to turn anteriorly after midline crossing through an attractive mechanism. Here we show that an atypical protein kinase C, PKCzeta, is required for Wnt attraction of commissural axons and proper anterior-posterior (A-P) pathfinding. PKCzeta pseudosubstrate and expression of a activation-defective PKCzeta mutant in commissural neurons caused A-P randomization in "open-book" explants. Upstream of PKCzeta, heterotrimeric G-protein and phosphatidylinositol-3-kinase (PI3K) signaling are required for A-P guidance. Inhibition of p110gamma using a kinase-defective construct resulted in A-P randomization. Remarkably, PI3Kgamma protein is localized specifically in the post-crossing segment of commissural axons, and overexpression of p110gamma, the catalytic subunit, caused precocious anterior turning of commissural axons before midline crossing. Therefore, atypical PKC signaling is required for proper A-P guidance and that an upstream regulator, PI3Kgamma, can act as a switch to turn on Wnt responsiveness during midline crossing.

Cellular Migration and Formation of Axons and Dendrites

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Publisher : Academic Press
ISBN 13 : 0128144076
Total Pages : 628 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Cellular Migration and Formation of Axons and Dendrites by : Bin Chen

Download or read book Cellular Migration and Formation of Axons and Dendrites written by Bin Chen and published by Academic Press. This book was released on 2020-06-13 with total page 628 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular Migration and Formation of Neuronal Connections, Second Edition, the latest release in the Comprehensive Developmental Neuroscience series, presents the latest information on the genetic, molecular and cellular mechanisms of neural development. This book provides a much-needed update that underscores 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 the formation of axons and dendrites and cellular migration. Features leading experts in various subfields as section editors and article authors Presents articles that have been peer reviewed to ensure accuracy, thoroughness and scholarship Includes coverage of mechanisms which regulate the formation of axons and dendrites and cellular migration Covers neural activity, from cell-intrinsic maturation, to early correlated patterns of activity

Molecular Biology of The Cell

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ISBN 13 : 9780815332183
Total Pages : 0 pages
Book Rating : 4.3/5 (321 download)

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Book Synopsis Molecular Biology of The Cell by : Bruce Alberts

Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Discovering the Brain

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Publisher : National Academies Press
ISBN 13 : 0309045290
Total Pages : 195 pages
Book Rating : 4.3/5 (9 download)

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Book Synopsis Discovering the Brain by : National Academy of Sciences

Download or read book Discovering the Brain written by National Academy of Sciences and published by National Academies Press. This book was released on 1992-01-01 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain ... There is no other part of the human anatomy that is so intriguing. How does it develop and function and why does it sometimes, tragically, degenerate? The answers are complex. In Discovering the Brain, science writer Sandra Ackerman cuts through the complexity to bring this vital topic to the public. The 1990s were declared the "Decade of the Brain" by former President Bush, and the neuroscience community responded with a host of new investigations and conferences. Discovering the Brain is based on the Institute of Medicine conference, Decade of the Brain: Frontiers in Neuroscience and Brain Research. Discovering the Brain is a "field guide" to the brainâ€"an easy-to-read discussion of the brain's physical structure and where functions such as language and music appreciation lie. Ackerman examines: How electrical and chemical signals are conveyed in the brain. The mechanisms by which we see, hear, think, and pay attentionâ€"and how a "gut feeling" actually originates in the brain. Learning and memory retention, including parallels to computer memory and what they might tell us about our own mental capacity. Development of the brain throughout the life span, with a look at the aging brain. Ackerman provides an enlightening chapter on the connection between the brain's physical condition and various mental disorders and notes what progress can realistically be made toward the prevention and treatment of stroke and other ailments. Finally, she explores the potential for major advances during the "Decade of the Brain," with a look at medical imaging techniquesâ€"what various technologies can and cannot tell usâ€"and how the public and private sectors can contribute to continued advances in neuroscience. This highly readable volume will provide the public and policymakersâ€"and many scientists as wellâ€"with a helpful guide to understanding the many discoveries that are sure to be announced throughout the "Decade of the Brain."

Guidance Cues in the Developing Brain

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Publisher : Springer Science & Business Media
ISBN 13 : 9783540001171
Total Pages : 174 pages
Book Rating : 4.0/5 (11 download)

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Book Synopsis Guidance Cues in the Developing Brain by : Ivica Kostovic

Download or read book Guidance Cues in the Developing Brain written by Ivica Kostovic and published by Springer Science & Business Media. This book was released on 2003-03-24 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many complex molecular interactions are involved in the development of the mammalian brain. Molecules serving as guidance cues for migratory cells, growing axons and for recognition of postsynaptic targets are a major topic for research because they are directly involved in the formation of neuronal circuits, thus creating the foundation for subsequent functional refinement through interactions with the environment. In addition, most guidance cue molecules are also involved in plasticity, damage repair and regeneration in the adult brain. This volume reviews current knowledge on major classes of molecules involved in: guidance of growing axons; tau proteins involved in the establishment of axonal polarity, outgrowth and contact recognition; gangliosides and lectins involved in neuronal migration, neurite outgrowth and contact recognition; and myelin molecules that inhibit nerve regeneration.

Cellular and Molecular Mechanisms of Axon Guidance in the Embryonic Vertebrate Brain

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ISBN 13 :
Total Pages : 490 pages
Book Rating : 4.:/5 (222 download)

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Book Synopsis Cellular and Molecular Mechanisms of Axon Guidance in the Embryonic Vertebrate Brain by : Richard B. Anderson

Download or read book Cellular and Molecular Mechanisms of Axon Guidance in the Embryonic Vertebrate Brain written by Richard B. Anderson and published by . This book was released on 1998 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: