Neurogenetics: Current Topics in Cellular and Developmental Neurobiology

Description

This textbook provides students with knowledge of neurogenetics, neurogenesis, neuronal specification and function, neuronal networks, learning and memory formation, brain evolution, and neurodegenerative diseases. Students are introduced to topics of classical developmental genetics as well as modern molecular and neurogenetic methods. Using a wealth of examples from current research, the textbook takes a strong applied approach. Using animal models such as Drosophila melanogaster and Caenorhabditis elegans as well as mammalian systems, the interrelationships between genes, neurons, nervous systems, and behaviour under normal and pathological conditions are illustrated. The textbook aims encourage students to address biological questions in neurogenetics and to think about the design of their own experiments. It targets primarily master and graduate students in neurobiology, but is also a valuable teaching tool for instructors in these fields. Preface Contents 1 Introduction to Neurogenetics 1.1 Definitions of Neurogenetics 1.2 Instrumental Versus Analytical Neurogenetics 1.3 History of Neurogenetics 1.4 Model Systems in Neurogenetics 1.4.1 Caenorhabditis elegans 1.4.2 Drosophila melanogaster 1.4.3 Vertebrate Animal Models 1.4.4 Human (Homo sapiens) References Further Reading 2 Neurogenetic Analysis in Caenorhabditis elegans 2.1 C. elegans Model for Neurobiology 2.1.1 A Powerful Genetic Model 2.1.2 Evolutionary Conservation of Neuronal Genes 2.1.3 The Architecture of the C. elegans Nervous System 2.1.4 The C. elegans Synaptic Connectome 2.1.5 C. elegans Behavioral Repertoire 2.1.6 Major Strengths of the Model 2.2 Experimental Approaches for the Neurogenetic Analysis of Genes and Neural Circuits in C. elegans 2.2.1 Genetic Screens 2.2.1.1 Mutagenesis Screen 2.2.1.2 Large-Scale RNAi Screen 2.2.2 Transgenic Approaches in C. elegans 2.2.2.1 Transgenesis in C. elegans 2.2.2.2 How to Target the Expression of a Transgene in a Specific Neuron Type 2.2.3 Gene Expression Analysis in the Nervous System 2.2.3.1 Gene Expression Analysis with Reporter 2.2.3.2 Neuron-specific Transcriptomics 2.2.3.3 Single-Cell RNA-seq to Learn About Every Cell Type in a Single Analysis 2.2.4 Gene Functional Analysis in the Nervous System 2.2.5 Circuit Functional Analysis 2.2.5.1 Monitoring Neuronal Activity 2.2.5.2 Upregulating Neuronal Activity 2.2.5.3 Downregulating Neuron Activity 2.3 Perspectives on Nervous System Function Analyses in C. elegans 2.3.1 Application of State-of-the-art Methods to Better Understand the Function of Gene, Neuron, Circuit, and Behavior 2.3.2 Integration of Multiple Methods to Bridge the Function of Genes, Neurons, and Circuits to Behavior 2.3.3 Development of Cost-Effective Novel Neurogenetic Tools 2.3.3.1 Gene Function 2.3.3.2 Neuron Function 2.3.3.3 Circuit Architecture and Function 2.3.4 Translational Prospects References (Owing to space limitations, the authors apologize that many articles that significantly contributed to C. elegans neurogenetics could not be cited.) 3 Regionalization of the Early Nervous System 3.1 Introduction 3.1.1 A Morphological Perspective 3.1.2 Neural Dorsoventral Patterning 3.1.2.1 Morphogenetic Gradients: Sog/Chordin and Dpp/BMP4 3.1.2.2 Columnar Genes: vnd/Nkx, ind/Gsh, and msh/Msx 3.1.3 Anteroposterior Organization of the Developing Brain 3.1.3.1 Cephalic Gap Genes Specify the Anterior Brain Territories 3.1.3.2 Homeotic Selector (Hox) Genes Specify Posterior Hindbrain Neuromeres 3.1.3.3 Tripartite Organization of the Urbilaterian Brain References 4 Early Neurogenesis and Gliogenesis in Drosophila 4.1 Introduction 4.2 Embryonic Neurogenesis in the Drosophila CNS 4.2.1 Neural Competence and Proneural Genes 4.2.2 Lateral Inhibition: Proneural Genes and Notch Signalling 4.2.3 Spatio-temporal Generation of Neuroblast Progeny 4.3 Gliogenesis in Drosophila 4.4 The GAL4-UAS System References 5 Neural Stem Cells and Brain Tumour Models in Drosophila 5.1 Introduction 5.2 Symmetric and Asymmetric Stem Cell Divisions 5.3 Polarity Cues Direct the Asymmetric Segregation of Cell-Fate Determinants 5.3.1 Mechanisms to Orient the Cell Division Axis 5.3.2 Proliferation and Termination of Neural Precursors 5.3.2.1 Type IA and Type ID Neuroblasts 5.3.2.2 Type II Neuroblasts 5.3.2.3 Mushroom Body Neuroblasts 5.3.2.4 Optic Lobe Neural Precursors 5.3.3 Techniques to Study Tumour Suppressor Gene and Oncogene Function in Genetic Mosaics 5.3.4 Mosaic Analysis with a Repressible Cell Marker (MARCM) 5.3.5 Mosaic Analysis with Flip-Out Clones 5.4 Brain Tumours Derived from Neuroblasts 5.4.1 Examples of Tumour Suppressor Genes Affecting Neuroblast Proliferation 5.4.2 Examples of Oncogenes Affecting Neuroblast Proliferation 5.4.2.1 atypical Proteinkinase C (aPKC) 5.4.2.2 Notch (N) 5.4.3 Misregulated Spindle Orientation Can Result in Neuroblast Overproliferation 5.5 Brain Tumours Derived from Neuroepithelial Cells 5.6 Models for Metastasis in Drosophila References 6 Eye Development in Drosophila: From Photoreceptor Specification to Terminal Differentiation 6.1 Drosophila as a Model Organism to Understand Eye Development 6.2 Morphology of the Drosophila Compound Eye 6.3 Determination of Eye and Antennal Fate in the Eye-Antennal Imaginal Disc 6.4 The Retinal Determination Cascade 6.5 Morphogenetic Furrow 6.6 Initiation of the Morphogenetic Furrow 6.7 Specification of R8 Photoreceptor Neuron 6.8 Recruitment of R1–R7 Photoreceptor Neurons 6.9 Initiation of Terminal Differentiation and Photoreceptor Subtype Specification 6.10 Specification of Inner Versus Outer Photoreceptor Subtypes 6.11 Stochastic Determination of Yellow Versus Pale Ommatidia 6.12 Specification of Photoreceptors in the Dorsal Rim Area (DRA) References 7 Neurogenetics of Memory, Learning, and Forgetting 7.1 Learning Is Essential for Survival 7.1.1 Non-associative Learning 7.1.1.1 Two Types of Non-associative Learning 7.1.1.2 Insights from Humans and Model Organisms: How Are Memories Stored in Nerve Cells? 7.1.1.3 Simple Behaviors can be Studied in Aplysia 7.1.1.4 Habituation in Invertebrates: Insights from Aplysia 7.1.1.5 Sensitization in Invertebrates: Insights from Aplysia 7.1.2 Associative Learning 7.1.2.1 Pavlov's Associative Learning Experiments 7.1.2.2 Associative Learning in Aplysia 7.1.2.3 Associative Learning in Drosophila 7.1.2.4 Operant Conditioning: A Way of Associative Learning 7.2 Memory 7.2.1 Explicit Memory 7.2.2 Implicit Memory 7.3 Mechanisms of Learning and Memory 7.3.1 Cellular Mechanisms 7.3.1.1 The Case of Henry Molaison 7.3.1.2 The Hippocampus as a Learning Center 7.3.1.3 Long-Term Potentiation as a Mechanism to Store Memories 7.3.1.4 Drosophila: A Model Organism to Map Neurons 7.3.1.5 Drosophila's Odor Learning Circuit 7.3.1.6 UAS-Gal4: A Binary Transcriptional System 7.3.1.7 The Mushroom Body Is the Fly's Central Structure for Learning 7.3.1.8 Shibire to Block Synaptic Transmission 7.3.1.9 The MB Synaptic Output Is Not Required During Memory Acquisition But It Is Necessary During Retrieval 7.3.2 Molecular Mechanisms 7.3.2.1 Seymour Benzer: Identifying Drosophila Melanogaster Learning Mutants 7.3.2.2 Drosophila Learning and Memory Genes 7.3.2.3 Molecular Mechanisms in Aplysia: Short-Term and Long-Term Sensitization 7.3.2.4 Enhancement Synaptic Efficacy 7.4 Forgetting 7.4.1 Active Forgetting Pathways References 8 Evolution and Origins of Nervous Systems 8.1 Basic Concepts of Evolution 8.1.1 Terminology and Representation of Evolutionary Relationships 8.1.2 Evo-Devo: A Set of Comparative Methods to Uncover Characteristics of Common Ancestors 8.2 Origin of Neurons and Synapses 8.2.1 The Evolution of Neurosecretory Proteins Predates the Emergence of Animals 8.2.2 Placozoans Are Animals Without Neurons but with Cells That Share Homologies with Synapses 8.2.3 Determining the Earliest-Branching Clade Is Crucial to Understand Evolution of Neurons 8.3 The Nerve Nets of Cnidarians 8.4 Centralization of the Nervous System in Bilaterians 8.4.1 The Study of Expression Domains Across Species Can Provide Information About CNS Origins 8.4.2 References 9 Embryonic Neurogenesis in the Mammalian Brain 9.1 Molecular and Cellular Mechanisms of Neural Development 9.1.1 Symmetric Versus Asymmetric Neural Stem Cell Division Modes 9.1.2 Proneural Genes in Vertebrate Nervous System Development 9.1.3 Notch Signalling in Vertebrate Nervous System Development 9.1.4 Oscillation of Hes and Proneural Factors 9.1.5 Cross-Regulation Between the Cell Cycle and Cell Fate 9.1.6 Spatiotemporal Generation of Postmitotic Neurons 9.2 Neural Stem Cell and Progenitor Cell Types in the Neocortex 9.2.1 Lissencephalic and Gyrencephalic Brains 9.2.2 Populations of Stem and Progenitor Cell Types in the Neocortex 9.2.2.1 Neuroepithelial Cells 9.2.2.2 Apical Radial Glial Cells (aRG) and Apical Intermediate Progenitors (aIP) 9.2.2.3 Basal Radial Glial Cells (bRG) and Basal Intermediate Progenitors (bIP) 9.2.3 Cellular Mechanisms of Neocortex Expansion References 10 Models of Neurodegenerative Diseases 10.1 Introduction 10.1.1 Alzheimer's Disease (AD) 10.1.1.1 Models of Alzheimer's Disease 10.1.2 Parkinson's Disease (PD) 10.1.2.1 Models of Parkinson's Disease 10.1.3 Amyotrophic Lateral Sclerosis (ALS) 10.1.3.1 Models of Amyotrophic Lateral Sclerosis 10.2 Use of Non-rodent Model Organisms in Neurodegenerative Disease 10.3 Use of iPSCs to Model Neurodegenerative Diseases References Index