Mouse Brain Development

From Spontaneous to Induced Neurological Mutations: A Personal Witness of the Ascent of the Mouse Model 1(20) Pasko Rakic Introduction 1(2) Beginning: The Values and Limits of Spontaneous Mutations 3(6) Renaissance: New Opportunities and Induced Mutations 9(5) Epilogue 14(7) References 15(6) Mapping Genes that Modulate Mouse Brain Development: A Quantitative Genetic Approach 21(30) Robert W. Williams Introduction 21(1) Why Brain Weight and Neuron Number Matter 22(2) Metabolic Constraints 22(1) Functional Correlates 22(1) Insights into CNS Development 23(1) Biometric Analysis of the Size and Structure of the Mouse CNS 24(3) Precedents 24(1) A New Opportunity 24(1) Brain Weight is Highly Variable 25(1) Sex and Age Effects on Brain Weight 25(2) Large Differences Between Substrains 27(1) Mapping Brain Weight QTLs 27(12) QTLs Versus Mendelian Loci 27(1) Assessing Trait Variation 27(2) Estimating Heritability 29(1) Phenotyping and Genotyping Members of an Experimental Cross 30(1) Phenotyping and Regression Analysis 31(2) Genotyping 33(1) The Statistics of Mapping QTLs 34(2) Permutation Analysis 36(2) Cloning QTLs 38(1) Probability of Success 38(1) Neuron and Glial Cell Numbers in Adult Mice 39(3) The Mouse Brain Library at http://nervenet.org/mbl/mbl/html 40(1) Numbers of Neurons and Glial Cells in the Brain of a Mouse 41(1) Mapping QTLs that Modulate Neuron Number 42(2) Mapping Cell-Specific QTLs 42(1) The Nncl Locus 42(1) Mechanisms of QTL Action 43(1) Candidate Gene Analysis 43(1) Conclusion 44(7) References 44(7) Genetic Interactions During Hindbrain Segmentation in the Mouse Embryo 51(40) Paul A. Trainor Miguel Manzanares Robb Krumlauf Introduction 51(4) Generation of Diversity in the Developing Nervous System 51(2) Segmental Organisation of the Hindbrain 53(2) Patterns of Gene Expression During Hindbrain Development 55(6) Hox Genes 55(3) Upstream Regulators of Hox Genes 58(1) Other Gene Families 59(2) Genetic Control of Hindbrain Patterning 61(8) Retinoic Acid Pathways 62(2) Krox20 Targets 64(2) Kreisler Targets 66(1) Hox Gene Auto- and Cross-Regulation 67(2) Mutational Analyses of Gene Function 69(7) Segmentation Genes 69(3) Segment Identity Genes 72(4) Mechanisms of Hindbrain Segmentation 76(1) Conclusions 77(14) References 78(13) Neurogenetic Compartments of the Mouse Diencephalon and some Characteristic Gene Expression Patterns 91(16) Salvador Martinez Luis Puelles Introduction 91(3) Origin and Definition of Diencephalon 94(2) Diencephalic Segmentation 96(2) Diencephalic Histogenetic Differentiation 98(1) Alar Plate Domains at E12.5 99(8) References 103(4) Neuronogenesis and the Early Events of the Neocortical Histogenesis 107(38) V. S. Caviness, Jr. T. Takahashi R. S. Nowakowski Introduction 107(2) The Neocortical Pseudostratified Ventricular Epithelium 109(2) Cytologic and Architectonic Features of the PVE 109(2) Neocortex as Outcome of Neuronogenesis in the PVE 111(4) The Radial Dimension of the Neocortex 113(1) The Tangential Dimensions of the Neocortex 114(1) The Proliferative Process Within the Murine Neocortical PVE 115(10) There are Two Stages of Proliferative Activity in the PVE (Fig. 2) 116(1) Neuron Production Advances in an Orderly Sequence 116(1) The Proliferative State of PVE Varies Across the Surface of the Neocortex 117(1) The Cell Cycle in Histogenesis 117(1) A General Quantitative Model of Neuron Production 118(3) Parameters of the Model: Experiments in Mouse 121 The Number of Integer Cycles 119(2) The Q and P Fractions 121(2) Neuron Production Model 123(2) Higher Order Neuronogenetic Control 125(6) Number of Cell Cycles Regulated by Q 126(1) Propagation of the Neuronogenetic Sequence Regulated by Tc 126(1) Propagation of Cell Cycle Domains 127(1) Initiation of Cycle at Origin 127(2) Propagation of Cycle Domains 129(2) The Proliferative Process and Histogenetic Specification 131(5) Cell Number, Cell Class and Laminar Fate 131(3) Regional Specification Within the PVE 134(2) The PVE: A Conserved Histogenetic Specification 136(9) References 138(7) Programmed Cell Death in Mouse Brain Development 145(18) Chia-Yi Kuan Richard A. Flavell Pasko Rakic Introduction 145(1) Conceptual Framework of Programmed Cell Death 145(2) Mechanistic Framework of Programmed Cell Death 147(1) Caspases-3 and -9 are Required for Developmental Apoptosis of Neurons 148(3) The Bcl-2 Proteins Family Has Both Proapoptotic and Antiapoptotic Effects 151(3) Apoptotic Defects in Founders and Postmitotic Neurons Have Distinct Consequences 154(2) c-Jun N-Terminal Kinases Regulate Brain Region-Specific Apoptosis 156(2) Concluding Remarks 158(5) References 160(3) Neurotrophic Factors: Versatile Signals for Cell-Cell Communication in the Nervous System 163(26) Carlos F. Ibanez Introduction 163(1) The Neurotrophic Hypothesis 164(3) Neurotrophic Factors 167(1) Beyond the Neurotrophic Hypothesis 168(3) Revisiting the Neurotrophic Hypothesis with Molecular Genetics. 171(2) Selective Neuronal Losses and Maturation Deficits Following Inactivation of Genes Encoding Neurotrophic Factors or Their Receptors 173(5) Neurotrophic Factors Regulate Target Invasion 178(3) BDNF as a Maturation Factor for the Cerebal Cortex 181(3) Conclusions 184(5) References 184(5) Growth Factor Influences on the Production and Migration of Cortical Neurons 189(28) Janice E. Brunstrom Alan L. Pearlman Introduction 189(1) Trophic Factor Influences on Neurogenesis in the Ventricular Zone 190(6) Neurotrophins 190(1) Fibroblast Growth Factors 191(3) Insulin-Like Growth Factors 194(1) Trophic Collaborations 195(1) Trophic Factor Influences on Glial-Guided Radial Migration 196(1) Trophic Factor Influences on Tangential Migration 197(3) NT4 Produces Heterotopic Accumulations of Neurons in the MZ in vitro 198(1) NT4, But not BDNF, Produces Heterotopias in a TrkB-Mediated Response 198(2) NT4 Also Produces Heterotopic Neuronal Collections in vivo 200(1) Pathogenesis of NT4-Induced Heterotopias 200(4) NT4 Does Not Induce Cell Proliferation in the Marginal Zone 201(1) NT4-Induced Heterotopias are Composed of Marginal Zone Neurons 202(1) NT4-Induced Accumulation of Neurons is not at the Expense of the Subplate 202(1) Heterotopic Neurons are not Misplaced Cortical Plate Cells 202(1) Heterotopias do not Result from the Trauma of Intraventricular Injection 203(1) Heterotopias are not Caused by Rescue of MZ Neurons from Cell Death 203(1) What is the Source of the Excess Neurons that Form NT4-Induced Heterotopias? 204(13) References 207(10) Signalling from Tyrosine Kinases in the Developing Neurons and Glia of the Mammalian Brain 217(24) Elena Cattaneo Massimo Gulisano Introduction 217(1) Tyrosine Kinases During CNS Development 218(3) Growth Factors and Their Cell Surface Receptors 218(3) Phospho-Tyrosines and Their SH2 Partners 221(2) Controlling the Activity of the Ras-MAPK Pathway 223(4) The Players 223(2) MAPK: Proliferation or Differentiation? 225(1) Changing Adaptors for the Ras-MAPK Pathway: The Shc(s) 226(1) Controlling Cell-Survival Via PI3K 227(2) The JAK/STAT Pathway: A New Route to Proliferation and Differentiation in the Brain 229(3) The Action of Phosphatases 232(1) Concluding Remarks 233(8) References 234(7) The Role of the p35/cdk5 Kinase in Cortical Development 241(14) Yong T. Kwon and Li-Huei Tsai Introduction 241(1) cdk5 241(1) p35 Family Members 242(1) Expression Patterns 243(1) Function of the cdk5 Kinase in Neurite Outgrowth 243(1) p35 and cdk5 Knockout Mice 244(3) p35/cdk5 and Reeler/Scrambler 247(1) Substrates 248(1) Regulation 248(1) Conclusion 249(6) References 251(4) The Reelin-Signaling Pathway and Mouse Cortical Development 255(22) Isabelle Bar Catherine Lambert de Rouvroit Andre M. Goffinet Introduction 255(1) Overview of Early Cortical Development in Normal Mice 255(3) The Preplate 257(1) Appearance of the Cortical Plate 257(1) Cortical Phenotype in Reeler Mutant Mice 258(4) Reelin (Reln) 262(6) The Reln Gene 262(3) Reln mRNA Expression During Cortical Development 265(1) Reln Protein 265(1) Studies of Reln Function 266(1) Reelin is Processed in vivo by a Metalloproteinase 266(1) Reln an Axonal Growth 267(1) Mouse Disabled1 and Scrambler/Yotari Mutations 268(3) Very Low Density Lipoprotein Receptor and Apolipoprote in E Receptor Type 2 271(6) References 274(3) The Subpial Granular Layer in the Developing Cerebral Cortex of Rodents 277(16) Gundela Meyer Rafael Castro Jose Miguel Soria Alfonso Fairen Introduction 277(2) Neuronal Populations of the Rodent Marginal Zone 279(6) Pioneer Neurons 279(2) The Subpial Granular Layer 281(3) Reelin-Expressing Cajal-Retzius Cells of Rodent Cortex 284(1) Possible Origin of the Rodent Subpial Granular Layer 285(1) Radial and Tangential Migration Pathways into the Cortex 286(2) Conclusions 288(5) References 289(4) Development of Thalamocortical Projections in Normal and Mutant Mice 293(40) Zoltan Molnar Anthony J. Hannan Introduction 293(1) Neurogenesis and Formation of Mammalian Cortical Plate 294(1) Introduction to Development of Thalamic Nuclei 295(1) Overview of Thalamocortical Projections in the Adult Mouse 296(1) Timing and Early Pattern of Thalamic Axon Outgrowth 296(5) The Waiting Period 298(1) Invasion of the Cortex and Establishment of Laminar Termination Patterns 299(2) The Thalamocortical Pathways are Modified in Regions Where Transient Cells are Located During Development 301(1) The Handshake Hypothesis 301(1) Introduction to the Development of Barrel Cortex 302(2) Mutant Mice Provide New Insights into Developmental Mechanisms 303(1) Axonal Pathfinding at the Cortico-Striatal Junction in Tbr-1, Gbx-2 and Pax-6 KO Mice 304(6) The reeler Mouse 305(1) The reeler Phenotype 305(1) The reeler Mutant Mouse as a Model System to Explore Mechanisms of Thalamocortical Development 305(4) The L1 KO Mouse 309(1) Possible Inhibitory Factory in and Around the Internal Capsule 309(1) Mutants with Disturbances in Thalamocortical Interactions 310(12) Barrel Formation in reeler Mouse 312(1) The Barrelless Mouse 313(1) The Barrelless Phenotype 313(1) Lack of Formation and Stabilisation of Barrel Patterns in the Mutant 314(1) Similar Areal Differences in Thalamocortical Innervation Patterns in Normal and Barrelless Mice 314(1) The MAO-A KO Mouse 315(1) The NMDA Receptor KO Mouse: Role of Activity in Barrel Formation 316(1) A Specific Postsynaptic Defect in Barrel Formation Identified in PLC-$1 Knockout mice 317(1) The GAP-43 KO Mouse 318(1) Overview of Mutant Mice with Barrelless Phenotypes 319(1) Mutations Indirectly Affecting Thalamocortical Development 319(1) Thalamocortical Topography in Anophthalmic Mutants and After Early Binocular Enucleation 320(1) Altered Thalamocortical Topography in Albinism and After Early Monocular Enucleation 321(1) Extranumery Vibrissae 322(1) Conclusions 322(11) References 323(10) Subject Index 333