Transcription Factors in the Nervous System – Development, Brain Function and Diseases

Since 1997 Gerald Thiel has been professor for Medical Biochemistry and Molecular Biology at the University of the Saarland, Germany. In 1987 he started his career as a post-doc at The Rockefeller University, New York, in the lab of the 2000 Nobel Prize Laureate Paul Greengard. At the same time he was visiting fellow at the Howard Hughes Medical Institute, University of Texas. In 1991 and 1992 he worked as an assistant professor for Molecular and Cellular Neuroscience at The Rockefeller University, and from 1992 to 1997 he was head of lab at the Institute for Genetics, University of Cologne, Germany. His current research interests are the regulation of neuronal gene transcription, signal transduction in the nervous system and the regulation of proliferation and programmed cell death in the nervous system.

Preface.List of Contributors.Color Plates.Part I Transcription Factors in Neural Development.1 Roles of Hes bHLH Factors in Neural Development (Ryoichiro Kageyama, Jun Hatakeyama, and Toshiyuki Ohtsuka).Abstract.1.1 Introduction.1.2 Structure and Transcriptional Activities of Hes Factors.1.3 Regulation of Hes Gene Expression.1.4 Expression of Hes Genes in the Developing Nervous System.1.5 Maintenance of Neural Stem Cells by Hes Genes.1.6 Promotion of Gliogenesis by Hes Genes.1.7 Maintenance of the Isthmic Organizer by Hes Genes.1.7 Perspective.Acknowledgments.Abbreviations.2 The Role of Pax6 in the Nervous System during Development and in Adulthood: Master Control Regulator or Modular Function? (Nicole Haubst, Jack Favor, and Magdalena Gotz).Abstract.2.1 Introduction.2.2 Molecular Features of Pax6.2.3 Function of Pax6 in Development.2.4 Function of Pax6 in the Adult Brain.2.5 Mechanisms of Pax6 Function.2.6 Conclusions and Outlook.Abbreviations.3 Phox2a and Phox2b: Essential Transcription Factors for Neuron Specification and Differentiation (Uwe Ernsberger and Hermann Rohrer).Abstract.3.1 Introduction.3.2 Molecular Characteristics of Phox2 Genes and Proteins.3.3 Physiological Relevance of Phox2 Transcription Factors.3.4 Molecular Mechanism of Action in Different Lineages. 3.5 Conclusions and Outlook.Acknowledgments.Abbreviations.4 Functions of LIM-Homeodomain Proteins in the Development of the Nervous System (Yangu Zhao, Nasir Malik, and Heiner Westphal).Abstract.4.1 Introduction.4.2 Common Structural Features and Classification of LIM-HD Proteins.4.3 LIM-HD Proteins and the Development of Invertebrate Nervous Systems.4.4 Functions of LIM-HD Proteins in the Development of Vertebrate Nervous Systems.4.5 Factors that Interact with LIM-HD Proteins.4.6 Downstream Targets of LIM-HD Proteins.4.7 Conclusion and Future Directions.Abbreviations.5 The Roles of Serum Response Factor in Brain Development and Function (Bernd Knoll and Alfred Nordheim).Abstract.5.1 Serum Response Factor as a Transcription Factor.5.2 Neuronal Expression Patterns of SRF and Partner Proteins.5.3 SRF Target Genes with Brain Functions.5.4 Essential Requirement for SRF in Neuronal Migration.5.5 SRF and Partner Proteins in Neurite Outgrowth and Axonal Guidance.5.6 SRF-Mediated Gene Expression in Learning and Memory.5.7 SRF in Neurological Disorders.5.8 Perspectives.Acknowledgments.Abbreviations.6 RE-1 Silencing Transcription Factor (REST): Regulation of Neuronal Gene Expression via Modification of the Chromatin Structure (Gerald Thiel and Mathias Hohl).Abstract.6.1 Tissue-Specific Gene Expression: The Molecular Basis for the Function of a Multicellular Organism.6.2 Modular Structure of REST.6.3 Biological Activity of REST.6.4 Mechanism of Transcriptional Repression by REST: Modulation of the Chromatin Structure.6.5 Lessons from the REST Knockout Mouse.6.6 Cell Type-Specific Regulation of REST Target Genes.6.7 The Role of REST in the Differentiation of Neural Stem Cells.6.8 Involvement of REST in Brain Dysfunction and Disease.6.9 Conclusion and Prospects.Acknowledgments.Abbreviations.7 Roles of Tlx1 and Tlx3 and Neuronal Activity in Controlling Glutamatergic over GABAergic Cell Fates (Qiufu Ma and Le-ping Cheng).Abstract.7.1 Introduction.7.2 The Dorsal Horn of the Spinal Cord.7.3 Neurogenesis in the Dorsal Spinal Cord.7.4 The Tlx Family of Homeobox Proteins.7.5 Tlx Gene Expression Marks Sensory Circuits.7.6 Tlx Genes Serve as Binary Switches between Glutamatergic and GABAergic Transmitter Phenotypes.7.7 Binary Decision between GABAergic and Glutamatergic Cell Fates is a Common Theme.7.8 Coupling of Generic Transmitter Phenotypes and Region-Specific Neuronal Identities.7.9 The Plasticity of Neurotransmitter Phenotypes.7.10 Summary and Unsolved Problems.Abbreviations.8 Transcriptional Control of the Development of Central Serotonergic Neurons (Zhou-Feng Chen and Yu-Qiang Ding).Abstract.8.1 Introduction.8.2 Transcription Factors in the Development of 5-HT Neurons.8.3 Transcription Factors Expressed in 5-HT Progenitor Cells.8.4 Transcription Factors Expressed in the Ventricular Zone and Postmitotic 5-HT Neurons.8.5 Transcription Factors Expressed in Postmitotic 5-HT Neurons.8.6 The Relationship between Lmx1b and Pet1.8.7 Conclusions.Abbreviations.9 Role of Nkx Homeodomain Factors in the Specification and Differentiation of Motor Neurons and Oligodendrocytes (Jun Cai and Mengsheng Qiu).Abstract.9.1 Introduction.9.2 Structural Features of Nkx Homeobox Genes Involved in Ventral Neural Patterning.9.3 Selective Expression of Nkx Homeobox Genes in the Ventral Neural Tube.9.4 Nkx Genes are Class II Components of the Homeodomain Protein Code for Ventral Neural Patterning and Cell Fate Specification.9.5 Nkx Genes Control the Fate Specification and Differentiation of Motor Neurons.9.6 The Role of Nkx Genes in Oligodendrocyte Development.Acknowledgments.Abbreviations.10 Sox Transcription Factors in Neural Development (Michael Wegner and C. Claus Stolt).Abstract.10.1 The Sox Family of Transcription Factors.10.2 Sox Proteins and Neural Competence.10.3 Sox Proteins and the Neuroepithelial Stem Cell.10.4 Sox Proteins and the Neural Crest Stem Cell.10.5 Sox Proteins in Neural Determination and Lineage Decisions.10.6 Sox Proteins in Glial Differentiation.10.7 Sox Proteins in Neuronal Differentiation.10.8 Sox Proteins and their Molecular Mode of Action.10.9 Conservation of Sox Protein Function in Nervous System Development.Acknowledgments.Abbreviations.Part II Transcription Factors in Brain Function.11 The Role of CREB and CBP in Brain Function (Angel Barco and Eric R. Kandel).Abstract.11.1 Introduction.11.2 The CREB Family of Transcription Factors.11.3 The CREB Binding Protein.11.4 The CREB Activation Pathway.11.5 Functions of the CREB Activation Pathway in the Nervous System.11.6 Dysregulation of CREB Function and Disease in the Nervous System.11.7 Conclusions.Abbreviations.12 CCAAT Enhancer Binding Proteins in the Nervous System: Their Role in Development, Differentiation, Long-Term Synaptic Plasticity, and Memory (Cristina M. Alberini).Abstract.12.1 The CCAAT Enhancer Binding Proteins (C/EBPs).12.2 The Role of C/EBPs in Development and Differentiation.12.3 The Role of C/EBPs in Synaptic Plasticity and Memory.Abbreviations.13 The Role of c-Jun in Brain Function (Gennadij Raivich and Axel Behrens).Abstract.13.1 Introduction.13.2 C-Jun Phosphorylation and Upstream Signaling.13.3 Development.13.4 Novelty, Learning and Memory, and Addiction.13.5 Seizures and Excitotoxicity.13.6 Ischemia, Stroke, and Brain Trauma.13.7 Axotomy.13.8 Conclusions.Abbreviations.14 Expression, Function, and Regulation of Transcription Factor MEF2 in Neurons (Zixu Mao and Xuemin Wang).Abstract.14.1 Introduction.14.2 The MEF2 Family of Transcription Factors.14.3 Expression of Mef2 in Neurons.14.4 Function of Mef2 in Neurons.14.5 Regulation of MEF2 in Neurons.14.6 Future Studies.Acknowledgments.Abbreviations.15 RORa: An Orphan that Staggers the Mind (Peter M. Gent and Bruce A. Hamilton).Abstract.15.1 Introduction.15.2 Identification and Biochemical Properties of RORa.15.3 Role of RORa in the Developing Cerebellum.15.4 Roles of RORa in Other Tissues.15.5 In-Vivo Identification of RORa Targets.15.6 Implication of RORa in SCA1 Disorder.15.7 Summary.Abbreviations.16 The Role of NF-kB in Brain Function (Barbara Kaltschmidt, Ilja Mikenberg, Darius Widera, and Christian Kaltschmidt).Abstract.16.1 Introduction.16.2 The NF-kB/Rel Family of Transcription Factors.16.3 Canonical NF-kB Activation.Acknowledgments.Abbreviations.17 Calcineurin/NFAT Signaling in Development and Function of the Nervous System (Isabella A. Graef, Gerald R. Crabtree, and Fan Wang).Abstract.17.1 Biochemistry of NFAT Signaling.17.2 Roles of NFAT Signaling in Axonal Outgrowth and Synaptogenesis.17.3 A Possible Role for NFAT Signaling in Defining Pathways for Both Vessels and Peripheral Nerves.17.4 Roles of NFAT Signaling in Later Development: Responses to Spontaneous Activity.17.5 The Role of NFAT in Neuronal Survival.17.6 Small Molecule Inhibitors of CaN are Powerful Probes of Neuronal Development.17.7 NFAT Signaling and Transcriptional Control in Human Disease.17.8 Conclusion.Abbreviations.18 Stimulus-Transcription Coupling in the Nervous System: The Zinc Finger Protein Egr-1 (Oliver G. Rossler, Luisa Stefano, Inge Bauer, and Gerald Thiel).Abstract.18.1 Introduction.18.2 Modular Structure of Egr-1.18.3 Intracellular Signaling Cascades Converging at the Egr-1 Gene.18.4 The Egr-1 Promoter.18.5 Lessons from Egr-1-Deficient Mice.18.6 Egr-1 Regulates Synaptic Plasticity in the Nervous System.18.7 Correlation Between Proliferation of Astrocytes and Egr-1 Biosynthesis.18.8 Egr-1: A "Pro-apoptotic Protein" for Neurons?18.9 Conclusions and Future Prospects.Acknowledgments.Abbreviations.Part III Transcription Factors in Neuronal Diseases.19 The Presenilin/g-Secretase Complex Regulates Production of Transcriptional Factors: Effects of FAD Mutations (Nikolaos K. Robakis and Philippe Marambaud).Abstract.19.1 Introduction.19.2 Processing of APP and FAD.19.3 The Presenilins.19.4 The Notch1 ICD (NICD) Mediates Transcriptional and Developmental Functions Associated with Notch1 Receptor.19.5 Transcriptional Function of the APP ICD (AICD).19.6 PS1 and b-Catenin-Mediated Transcription.19.7 PS1 is a Critical Regulator of Cadherin-Dependent Cell-Cell Adhesion and Signal Transduction.19.8 Conclusions.Abbreviations.20 Transcriptional Abnormalities in Huntington's Disease (Dimitri Krainc).Abstract.20.1 Introduction.20.2 Mutant Huntingtin Interferes with Specific Components of General Transcriptional Machinery.20.3 Mutant Huntingtin Disrupts Sp1-TAF4 Transcriptional Pathway.20.4 Deregulation of CRE-Dependent Transcription in HD.20.5 Summary.Abbreviations.Acknowledgments.Index.