Mouse Brain Development

From Spontaneous to Induced Neurological Mutations: A Personal Witness of the Ascent of the Mouse Model.- 1 Introduction.- 2 Beginning: The Values and Limits of Spontaneous Mutations.- 3 Renaissance: New Opportunities and Induced Mutations.- 4 Epilogue.- References.- Mapping Genes that Modulate Mouse Brain Development: A Quantitative Genetic Approach.- 1 Introduction.- 2 Why Brain Weight and Neuron Number Matter.- 2.1 Metabolic Constraints.- 2.2 Functional Correlates.- 2.3 Insights into CNS Development.- 3 Biometric Analysis of the Size and Structure of the Mouse CNS.- 3.1 Precedents.- 3.2 A New Opportunity.- 3.3 Brain Weight is Highly Variable.- 3.4 Sex and Age Effects on Brain Weight.- 3.5 Large Differences Between Substrains.- 4 Mapping Brain Weight QTLs.- 4.1 QTLs Versus Mendelian Loci.- 4.2 Step 1: Assessing Trait Variation.- 4.3 Step 2: Estimating Heritability.- 4.4 Step 3: Phenotyping and Genotyping Members of an Experimental Cross.- 4.4.1 Phenotyping and Regression Analysis.- 4.4.2 Genotyping.- 4.5 Step 4: The Statistics of Mapping QTLs.- 4.5.1 Permutation Analysis.- 4.6 Cloning QTLs.- 4.7 Probability of Success.- 5 Neuron and Glial Cell Numbers in Adult Mice.- 5.1 The Mouse Brain Library at http://nervenet.org/mbl/mbl/html.- 5.2 Numbers of Neurons and Glial Cells in the Brain of a Mouse.- 6 Mapping QTLs that Modulate Neuron Number.- 6.1 Mapping Cell-Specific QTLs.- 6.2 The Nncl Locus.- 6.3 Mechanisms of QTL Action.- 6.4 Candidate Gene Analysis.- 7 Conclusion.- References.- Genetic Interactions During Hindbrain Segmentation in the Mouse Embryo.- 1 Introduction.- 1.1 Generation of Diversity in the Developing Nervous System.- 1.2 Segmental Organisation of the Hindbrain.- 2 Patterns of Gene Expression During Hindbrain Development.- 2.1 Hox Genes.- 2.2 Upstream Regulators of Hox Genes.- 2.3 Other Gene Families.- 3 Genetic Control of Hindbrain Patterning.- 3.1 Retinoic Acid Pathways.- 3.2 Krox20 Targets.- 3.3 Kreisler Targets.- 3.4 Hox Gene Auto- and Cross-Regulation.- 4 Mutational Analyses of Gene Function.- 4.1 Segmentation Genes.- 4.2 Segment Identity Genes.- 5 Mechanisms of Hindbrain Segmentation.- 6 Conclusions.- References.- Neurogenetic Compartments of the Mouse Diencephalon and some Characteristic Gene Expression Patterns.- 1 Introduction.- 2 Origin and Definition of Diencephalon.- 3 Diencephalic Segmentation.- 4 Diencephalic Histogenetic Differentiation.- 5 Alar Plate Domains at E12.5.- References.- Neuronogenesis and the Early Events of the Neocortical Histogenesis.- 1 Introduction.- 2 The Neocortical Pseudostratified Ventricular Epithelium.- 2.1 Cytologic and Architectonic Features of the PVE.- 3 Neocortex as Outcome of Neuronogenesis in the PVE.- 3.1 The Radial Dimension of the Neocortex.- 3.2 The Tangential Dimensions of the Neocortex.- 4 The Proliferative Process Within the Murine Neocortical PVE.- 4.1 There are Two Stages of Proliferative Activity in the PVE (Fig. 2).- 4.2 Neuron Production Advances in an Orderly Sequence.- 4.3 The Proliferative State of PVE Varies Across the Surface of the Neocortex.- 4.4 The Cell Cycle in Histogenesis.- 4.5 A General Quantitative Model of Neuron Production.- 4.6 Parameters of the Model: Experiments in Mouse.- 4.6.1 The Number of Integer Cycles.- 4.6.2 The Q and P Fractions.- 4.6.3 Neuron Production Model.- 5 Higher Order Neuronogenetic Control.- 5.1 Number of Cell Cycles Regulated by Q.- 5.2 Propagation of the Neuronogenetic Sequence Regulated by Tc.- 5.3 Propagation of Cell Cycle Domains.- 5.3.1 Initiation of Cycle at Origin.- 5.3.2 Propagation of Cycle Domains.- 6 The Proliferative Process and Histogenetic Specification.- 6.1 Cell Number, Cell Class and Laminar Fate.- 6.2 Regional Specification Within the PVE.- 7 The PVE: A Conserved Histogenetic Specification.- References.- Programmed Cell Death in Mouse Brain Development.- 1 Introduction.- 2 Conceptual Framework of Programmed Cell Death.- 3 Mechanistic Framework of Programmed Cell Death.- 4 Caspases-3 and -9 are Required for Developmental Apoptosis of Neurons.- 5 The Bcl-2 Proteins Family Has Both Proapoptotic and Antiapoptotic Effects.- 6 Apoptotic Defects in Founders and Postmitotic Neurons Have Distinct Consequences.- 7 c-Jun N-Terminal Kinases Regulate Brain Region-Specific Apoptosis.- 8 Concluding Remarks.- References.- Neurotrophic Factors: Versatile Signals for Cell-Cell Communication in the Nervous System.- 1 Introduction.- 2 The Neurotrophic Hypothesis.- 3 Neurotrophic Factors.- 4 Beyond the Neurotrophic Hypothesis.- 5 Revisiting the Neurotrophic Hypothesis with Molecular Genetics.- 6 Selective Neuronal Losses and Maturation Deficits Following Inactivation of Genes Encoding Neurotrophic Factors or Their Receptors.- 7 Neurotrophic Factors Regulate Target Invasion.- 8 BDNF as a Maturation Factor for the Cerebal Cortex.- 9 Conclusions.- References.- Growth Factor Influences on the Production and Migration of Cortical Neurons.- 1 Introduction.- 2 Trophic Factor Influences on Neurogenesis in the Ventricular Zone.- 2.1 Neurotrophins.- 2.2 Fibroblast Growth Factors.- 2.3 Insulin-Like Growth Factors.- 2.4 Trophic Collaborations.- 3 Trophic Factor Influences on Glial-Guided Radial Migration.- 4 Trophic Factor Influences on Tangential Migration.- 4.1 NT4 Produces Heterotopic Accumulations of Neurons in the MZ in vitro.- 4.2 NT4, But not BDNF, Produces Heterotopias in a TrkB-Mediated Response.- 4.3 NT4 Also Produces Heterotopic Neuronal Collections in vivo.- 5 Pathogenesis of NT4-Induced Heterotopias.- 5.1 NT4 Does Not Induce Cell Proliferation in the Marginal Zone.- 5.2 NT4-Induced Heterotopias are Composed of Marginal Zone Neurons.- 5.3 NT4-Induced Accumulation of Neurons is not at the Expense of the Subplate.- 5.4 Heterotopic Neurons are not Misplaced Cortical Plate Cells.- 5.5 Heterotopias do not Result from the Trauma of Intraventricular Injection.- 5.6 Heterotopias are not Caused by Rescue of MZ Neurons from Cell Death.- 6 What is the Source of the Excess Neurons that Form NT4-Induced Heterotopias?.- References.- Signalling from Tyrosine Kinases in the Developing Neurons and Glia of the Mammalian Brain.- 1 Introduction.- 2 Tyrosine Kinases During CNS Development.- 2.1 Growth Factors and Their Cell Surface Receptors.- 3 Phospho-Tyrosines and Their SH2 Partners.- 4 Controlling the Activity of the Ras-MAPK Pathway.- 4.1 The Players.- 4.2 MAPK: Proliferation or Differentiation?.- 4.3 Changing Adaptors for the Ras-MAPK Pathway: The Shc(s).- 5 Controlling Cell-Survival Via PI3K.- 6 The JAK/STAT Pathway: A New Route to Proliferation and Differentiation in the Brain.- 7 The Action of Phosphatases.- 8 Concluding Remarks.- References.- The Role of the p35/cdk5 Kinase in Cortical Development.- 1 Introduction.- 2 cdk5.- 3 p35 Family Members.- 4 Expression Patterns.- 5 Function of the cdk5 Kinase in Neurite Outgrowth.- 6 p35 and cdk5 Knockout Mice.- 7 p35/cdk5 and Reeler/Scrambler.- 8 Substrates.- 9 Regulation.- 10 Conclusion.- References.- The Reelin-Signaling Pathway and Mouse Cortical Development.- 1 Introduction.- 2 Overview of Early Cortical Development in Normal Mice.- 2.1 The Preplate.- 2.2 Appearance of the Cortical Plate.- 3 Cortical Phenotype in Reeler Mutant Mice.- 4 Reelin (Rein).- 4.1 The Reln Gene.- 4.2 Reln mRNA Expression During Cortical Development.- 4.3 Reln Protein.- 4.4 Studies of Reln Function.- 4.5 Reelin is Processed in vivo by a Metalloproteinase.- 4.6 Reln an Axonal Growth.- 5 Mouse Disabled1 and Scrambler/Yotari Mutations.- 6 Very Low Density Lipoprotein Receptor and Apolipoprote in E Receptor Type 2.- References.- The Subpial Granular Layer in the Developing Cerebral Cortex of Rodents.- 1 Introduction.- 2 Neuronal Populations of the Rodent Marginal Zone.- 2.1 Pioneer Neurons.- 2.2 The Subpial Granular Layer.- 2.3 Reelin-Expressing Cajal-Retzius Cells of Rodent Cortex.- 3 Possible Origin of the Rodent Subpial Granular Layer.- 4 Radial and Tangential Migration Pathways into the Cortex.- 5 Conclusions.- References.- Development of Thalamocortical Projections in Normal and Mutant Mice.- 1 Introduction.- 2 Neurogenesis and Formation of Mammalian Cortical Plate.- 3 Introduction to Development of Thalamic Nuclei.- 4 Overview of Thalamocortical Projections in the Adult Mouse.- 5 Timing and Early Pattern of Thalamic Axon Outgrowth.- 5.1 The Waiting Period.- 5.2 Invasion of the Cortex and Establishment of Laminar Termination Patterns.- 6 The Thalamocortical Pathways are Modified in Regions Where Transient Cells are Located During Development.- 6.1 The Handshake Hypothesis.- 7 Introduction to the Development of Barrel Cortex.- 7.1 Mutant Mice Provide New Insights into Developmental Mechanisms.- 8 Axonal Pathfinding at the Cortico-Striatal Junction in Tbr-1, Gbx-2 and Pax-6 KO Mice.- 8.1 The reeler Mouse.- 8.1.1 The reeler Phenotype.- 8.1.2 The reeler Mutant Mouse as a Model System to Explore Mechanisms of Thalamocortical Development.- 8.2 The L1 KO Mouse.- 8.2.1 Possible Inhibitory Factory in and Around the Internal Capsule.- 9 Mutants with Disturbances in Thalamocortical Interactions.- 9.1 Barrel Formation in reeler Mouse.- 9.2 The Barrelless Mouse.- 9.2.1 The Barrelless Phenotype.- 9.2.2 Lack of Formation and Stabilisation of Barrel Patterns in the Mutant.- 9.2.3 Similar Areal Differences in Thalamocortical Innervation Patterns in Normal and Barrelless Mice.- 9.3 The MAO-A KO Mouse.- 9.4 The NMDA Receptor KO Mouse: Role of Activity in Barrel Formation.- 9.5 A Specific Postsynaptic Defect in Barrel Formation Identified in PLC-?1 Knockout mice.- 9.6 The GAP-43 KO Mouse.- 9.7 Overview of Mutant Mice with Barrelless Phenotypes.- 10 Mutations Indirectly Affecting Thalamocortical Development.- 10.1 Thalamocortical Topography in Anophthalmic Mutants and After Early Binocular Enucleation.- 10.2 Altered Thalamocortical Topography in Albinism and After Early Monocular Enucleation.- 10.3 Extranumery Vibrissae.- 11 Conclusions.- References.