Development

Division.- 3.3 The C. crescentus Flagellum Is Similar to other Bacterial Flagelli.- 3.3.1 The Structure of the Flagellum Is Complex.- 3.3.2 Flagellar Gene Organization.- 3.3.3 Flagellar Assembly Proceeds from the Inside to the Outside.- 3.4 Transcription Controls Timing and Level of Flagellar Gene Expression.- 3.4.1 Alternate Promoters and a Variety of Regulatory Factors.- 3.4.2 Regulatory Hierarchy.- 3.4.3 Timing.- 3.5 Gene Products Are Segregated to the Appropriate Daughter Cell.- 3.5.1 Flagellins.- 3.5.2 Chemotaxis Proteins.- 3.5.3 Pilin.- 3.5.4 Heat-Shock Proteins.- 3.6 Mutations and Antibiotics with Pleiotropic Effects Define Dependent Pathways and Common Developmental Steps.- 3.7 Environmental Influences on C. crescentus.- 3.8 Outlook.- 3.9 Summary.- References.- 4 Streptomyces coelicolor: a Mycelial, Spore-Bearing Prokaryote.- 4.1 Introduction.- 4.2 Physiological Aspects of Early Events in Streptomyces Differentiation.- 4.2.1 Is There an Universal First Signal for Differentiation in Streptomyces?.- 4.2.2 Pheromones and Differentiation in Streptomyces spp..- 4.3 Genes Involved in Streptomyces Differentiation - an Overview.- 4.3.1 The Use of Streptomyces coelicolor for Genetic Studies.- 4.3.2 What Genes are Switched On in Response to the Signals for Initiation of Differentiation?.- 4.4 Development and Metamorphosis of the Aerial Mycelium.- 4.4.1 The Emergence of Aerial Hyphae.- 4.4.2 Overview of Sporulation of Aerial Hyphae and Its Genetic Control in S. coelicolor.- 4.4.3 The Crucial Role of a Transcription Factor in the Onset of Sporulation.- 4.4.4 Not All Sporulation Genes Depend on whiG for Expression.- 4.4.5 RNA Polymerase Diversity in S. coelicolor and Its Relevance to Differentiation.- 4.4.6 The Spore Pigment Locus whiE As a Potential Tool in Analysing Spore Development.- 4.4.7 A Role for Sigma-WhiG in Physiological Regulation?.- 4.5 Implications.- 4.6 Outlook.- 4.7 Summary.- References.- 5 The Programme of Cell Type Determination in Fission Yeast.- 5.1 Introduction.- 5.2 Life Cycle.- 5.2.1 Asexual Life Cycle.- 5.2.2 Sexual Life Cycle: Evidence for Three Cell Types.- 5.3 mat 1 Locus and the Cell types.- 5.4 Mating Type Switching: Homothallism Versus Heterothallism.- 5.5 The Programme of Switching.- 5.6 The Mating Type Region.- 5.7 "Position-Effect" Control for Expression and Switching of Cassettes.- 5.8 Trans-acting switch Genes.- 5.9 The Programme of Switching Is Dictated by Parental DNA Chain Inheritance.- 5.10 Comparison of S. pombe with S. cerevisiae Mating Type Interconversion.- 5.11 Outlook.- 5.12 Summary.- References.- 6 Development in Neurospora crassa.- 6.1 Introduction.- 6.2 Life Cycle.- 6.3 Microbiological and Genetic Techniques.- 6.4 Morphological Studies.- 6.4.1 From Spore to Mycelium.- 6.4.2 From Mycelium to Conidia.- 6.4.3 The Sexual Cycle.- 6.5 Influence of the Environment on Development.- 6.5.1 Environmental Factors Identified So Far.- 6.5.2 The Biological Meaning of Environmental Influence on Development.- 6.6 Developmental Genes of Neurospora.- 6.6.1 Biosynthetic and Developmental Pathways Have Little in Common.- 6.6.2 About the Pleiotropism of Developmentally Relevant Genes.- 6.6.3 On the Role of Mitochondria in Development.- 6.7 The Carbohydrate Pathways and Development.- 6.8 Molecular Biology.- 6.8.1 The Mating Type Locus.- 6.8.2 Gene Regulation During Conidiation.- 6.8.3 Blue Light Regulates Many Genes.- 6.9 Outlook.- 6.10 Summary.- References.- 7 Genetic Regulation of Sporulation in the Fungus Aspergillus nidulans.- 7.1 Introduction.- 7.2 Conidiation in the Wild type.- 7.2.1 General Considerations.- 7.2.2 Induction of Conidiation.- 7.2.3 Morphological Alterations.- 7.3 Molecular Genetic Facilities.- 7.3.1 Mutation.- 7.3.2 Complementation.- 7.3.3 Strain Construction and Genetic Mapping.- 7.3.4 DNA-Mediated Transformation.- 7.4 How Many Genes Are Needed for Growth and Development?.- 7.5 Analysis of Development with Stage-Specific Mutants.- 7.5.1 Mutants of Interest.- 7.5.2 Mutants Found but Ignored.- 7.5.3 Mutants Expected but Not Found.- 7.6 Characteristics of Important Developmental Mutants.- 7.6.1 General Considerations.- 7.6.2 Velvet Mutants.- 7.6.3 Fluffy Mutants.- 7.6.4 Aconidial Mutants.- 7.6.5 Bristle Mutants.- 7.6.6 Abacus Mutants.- 7.6.7 Stunted Mutants.- 7.6.8 Medusa Mutants.- 7.6.9 Ivory (Conidiophore Pigment) Mutants.- 7.6.10 Rodletless Mutants.- 7.6.11 Benomyl-Resistant Mutants.- 7.6.12 Wet-White Mutants.- 7.6.13 Spore Color Mutants.- 7.7 Molecular Analysis of Developmental Regulation.- 7.7.1 General Considerations.- 7.7.2 Isolation and Characterization of Regulatory Genes.- 7.7.3 Isolation and Characterization of Responder Genes.- 7.7.4 Controlled Induction of Regulatory Genes.- 7.8 Comparisons with Other Systems.- 7.9 Outlook.- 7.10 Summary.- References.- 8 Development of Trypanosomes.- 8.1 Introduction.- 8.1.1 Why Study Parasites?.- 8.1.2 Trypanosoma and Leishmania Species.- 8.1.3 The Life Cycle of Trypanosoma brucei.- 8.2 Trypanosomes as an Experimental System.- 8.2.1 Trypanosoma and Leishmania - in Vitro and in Vivo Cultivation Are Practical in the Laboratory.- 8.2.2 Energy Metabolism and Respiration in Trypanosoma and Leishmania Species.- 8.2.3 The Nuclei of Trypanosoma and Leishmania Species Have Unusual Properties.- 8.2.4 Trypanosomes Have a Special Mechanism of RNA Processing..- 8.2.5 The Expression of VSG Proteins Is Vital to the Bloodstream Form of African Trypanosomes.- 8.2.6 Differentiation of the Mitochondrion of T. brucei Occurs During Development.- 8.2.7 The Mitochondrial DNA of Trypanosoma and Leishmania Are Organized into Kinetoplasts.- 8.2.8 kDNA Sequences Participate in RNA Editing.- 8.3 Outlook.- 8.3.1 Mitochondrial Development - How Is It Triggered?.- 8.3.2 How Is RNA Editing Developmentally Regulated?.- 8.4 Summary.- References.- 9 Dictyostelium: From Unicellularity to Multicellularity.- 9.1 Introduction.- 9.2 Development of Dictyostelium discoideum.- 9.2.1 Cell-Cell Communication.- 9.2.2 Cell-Cell Adhesion.- 9.2.3 Multicellular Development.- 9.3 Molecular Analysis of Development.- 9.3.1 Cyclic AMP: a Morphoregulatory Signal.- 9.3.2 DIF: a Histospecific Regulatory Signal.- 9.4 Molecular Genetic Analysis of Aggregation.- 9.4.1 Essential Genes in Cell-Cell Communication.- 9.4.2 Cell Adhesion and Motility.- 9.5 Multicellular Development: Determining the Time of Cell Divergence.- 9.5.1 Diffusible Signals, Cell Differentiation and Pattern Formation.- 9.5.2 Cell Adhesion and the Control of Development.- 9.6 Outlook.- 9.7 Summary.- References.- 10 Control of the Cell Cycle in Yeasts.- 10.1 Introduction.- 10.2 Yeast Cell Cycles.- 10.2.1 Cell Cycle Mutants.- 10.2.2 Genes and Clones.- 10.3 Start.- 10.3.1 Pathways in the S. cerevisiae Cell Cycle.- 10.3.2 Start and Commitment.- 10.3.3 Growth Control.- 10.3.4 "Start" in Other Cells?.- 10.4 Coordination of Growth and Division.- 10.4.1 S. cerevisiae.- 10.4.2 S. pombe.- 10.4.3 Size Controls in G1 or G2.- 10.4.4 Size Control in Other Cells.- 10.5 The G2-Mitosis Transition.- 10.5.1 Regulation of the cdc2 Protein Kinase p34.- 10.5.2 MPF and Cyclins.- 10.6 Dependency of Mitosis on Prior DNA Replication.- 10.6.1 S. pombe.- 10.6.2 S. cerevisiae.- 10.7 Pathways in Mitosis.- 10.7.1 Pathways Within Mitosis.- 10.7.2 Dependency of S Phase on Prior Mitosis.- 10.8 Outlook.- 10.9 Summary.- References.- 11 Orcadian Rhythms of Neurospora.- 11.1 Introduction.- 11.1.1 The Neurospora Conidiation Rhythm - an Example of a Synchronized Developmental Event.- 11.2 Input.- 11.2.1 Responses to Light.- 11.2.2 Temperature Effects.- 11.3 The Strategies and Experiments Pursued Towards Understanding the Oscillator.- 11.3.1 The Genetic Approach: Strategies.- 11.3.2 The Biochemical Approach: Strategies.- 11.4 Output.- 11.4.1 Rhythmic Variables.- 11.5 Outlook - Possible Insights into Developmental Events from Studies on the Clock Mechanism.- 11.6 Summary.- References.- Section 2 Plants.- 12 Regulation of Development in the Moss, Physcomitrella patens.- 12.1 Introduction.- 12.1.1 The Suitability of Physcomitrella patens for the Study of Plant Development.- 12.1.2 Development of Physcomitrella patens.- 12.2 Techniques.- 12.2.1 Culture Methods.- 12.2.2 Genetic Methods.- 12.3 The Environmental Modification of Development.- 12.3.1 The Effect of Light.- 12.3.2 The Effect of Nutritional Status.- 12.3.3 The Effect of Phytohormones (Plant Growth Regulators).- 12.4 The Roles of Auxin and Cytokinin in Moss Development.- 12.4.1 Mutants Altered in Hormone Synthesis and Response.- 12.4.2 Continuous Medium Feeding with Auxins and Cytokinins.- 12.5 Tropic Responses.- 12.5.1 Phototropism.- 12.5.2 Gravitropism.- 12.6 Outlook.- 12.7 Summary.- References.- 13 Plant Photoperception: the Phytochrome System.- 13.1 Introduction.- 13.2 Plant Growth and Development Are Responsive to Light Cues.- 13.3 Plant Regulatory Photoreceptors: the UV-B, UV-A/Blue, and Red/Far Red Responsive Systems.- 13.4 Phytochrome Biological Activity.- 13.5 The Molecular Properties of Phytochrome.- 13.6 Photoequilibrium and Regulation of Phytochrome Abundance by Differential Stability.- 13.7 Distribution of Phytochrome.- 13.8 Intracellular Localization of Phytochrome Is Dependent upon Its Conformation.- 13.9 There Are Multiple Types of Phytochrome in Higher Plants.- 13.10 Phytochrome Regulates Plant Gene Expression.- 13.11 Autoregulation of the Phytochrome mRNA.- 13.12 Approaches to the Analysis of Phytochrome Signal Transduction.- 13.13 Outlook.- 13.14 Summary.- References.- 14 Exploration of Agrobacterium tumefaciens.- 14.1 Introduction.- 14.2 Exploration of Agrobacterium tumefaciens.- 14.2.1 Virulence, Function, and Induction.- 14.2.2 T-DNA Transfer.- 14.2.3 Integration of T-DNA.- 14.2.4 T-DNA Expression.- 14.2.5 Host Range.- 14.3 Outlook and Summary.- References.- 15 Exploitation of Agrobacterium tumefaciens.- 15.1 Introduction.- 15.2 T-DNA, a Universal Tool of Plant Molecular Biology.- 15.2.1 Recombination-Based Ti Plasmid Vectors.- 15.2.2 Binary Vectors.- 15.3 Gene Transfer and Transgenic Plant Technology.- 15.4 Gene Expression in Plants.- 15.5 Studying Gene Regulation by Chimeric Plant Promoters.- 15.6 Insertional Mutagenesis: a Link Between Classical and Molecular Plant Genetics.- 15.7 Outlook.- 15.8 Summary.- References.- 16 Developmental Genetics of Arabidopsis.- 16.1 Introduction.- 16.1.1 Biology of Arabidopsis.- 16.2 Genetics in Arabidopsis.- 16.2.1 Classical Genetics.- 16.2.2 Physical and RFLP Maps of Arabidopsis.- 16.3 Molecular Biology of Arabidopsis.- 16.3.1 Genome Size and Organization.- 16.3.2 Gene Transfer in Arabidopsis.- 16.4 Combining Genetics and Molecular Biology to Study Development in Arabidopsis.- 16.4.1 Insertional Mutagenesis Using Agrobacterium.- 16.4.2 Confirmation of Gene Identity by Complementation.- 16.5 Developmental Systems Presently Under Study in Arabidopsis.- 16.5.1 Genetics of Arabidopsis Embryo Development.- 16.5.2 Arabidopsis Phytohormone Mutants.- 16.5.3 Mutants of Arabidopsis That Alter Trichome Development.- 16.5.4 Genetic Analysis of Floral Development in Arabidopsis.- 16.5.5 Development of Roots in Arabidopsis.- 16.6 Outlook.- 16.7 Summary.- References.- 17 Homeotic Genes in the Genetic Control of Flower Morphogenesis in Antirrhinum majus.- 17.1 Introduction.- 17.2 Normal Flower Development.- 17.2.1 General Rules of Normal Flower Development in Higher Plants.- 17.2.2 Determination of Organ Identity During Sequential Organ Initiation.- 17.2.3 Flower Morphogenesis in Antirrhinum majus.- 17.3 Abnormal Flower Development.- 17.3.1 Analysis of Homeosis Can Help to Unravel the Rules Underlying Morphogenesis.- 17.3.2 Three Types of Homeotic Genes Control the Establishment of Flower Organ Identity.- 17.3.3 Differential Induction of Two Pathways Determine Four Organs: a Model.- 17.4 The Role of the deficiens Gene in Floral Organogenesis.- 17.4.1 Morphological Observations on Three Morphoalleles.- 17.4.2 Instability of deficiensglobifera.- 17.4.3 Homeotic Genes Encode Transcription Factors: the MADS-Box.- 17.4.4 Homology Between Floral Homeotic Genes.- 17.4.5 Homeotic Genes Are Upregulated in Two Whorls: Transcriptional Control.- 17.4.6 Posttranslational Processes Specify Homeotic Gene Functions.- 17.5 Outlook.- 17.6 Summary.- References.- 18 The Rhizobium-Legume Symbiosis.- 18.1 Introduction.- 18.1.1 Why Study Nodules?.- 18.2 The Two Symbiotic Partners.- 18.2.1 Rhizobia.- 18.2.2 Rhizobium Genetics.- 18.2.3 Legumes.- 18.2.4 Legume Genetics.- 18.3 Nodule Development.- 18.3.1 Preinfection Events.- 18.3.2 Infection.- 18.3.3 Bacterial Release.- 18.3.4 Nodule Maturation.- 18.3.5 Promoter Structure and Tissue-Specific Gene Expression.- 18.4 Cell to Cell Communication and Gene Expression in Development.- 18.4.1 Cell to Cell Contact.- 18.4.2 Diffusible Signals.- 18.4.3 Physiological Effects.- 18.5 Outlook.- 18.6 Summary.- References.- Section 3 Animals.- 19 Embryogenesis in Caenorhabditis elegans.- 19.1 Introduction.- 19.1.1 The C. elegans Life Cycle Is Rapid and Laboratory Culture Is Simple.- 19.1.2 Each Cell of a Worm Can be Identified Microscopically.- 19.1.3 A Large Number of C. elegans Genes Have Been Identified and Mapped.- 19.1.4 Rapidly Developing Molecular Genetics Provides Tools for Molecular Analysis.- 19.2 An Overview of Embryogenesis.- 19.2.1 Gametogenesis in G elegans Occurs in a Linear Spatial Progression.- 19.2.2 Fertilization Events Designate Anterior-Posterior Polarity.- 19.2.3 Early Cleavages Create Six Founder Cells.- 19.2.4 Further Embryogenesis Consists of Gastrulation, Cell Proliferation, and Morphogenesis.- 19.3 Determination of Cell Fate: Manipulation of Normal Embryos.- 19.3.1 Chromosomal Imprinting Does Not Appear to Affect Cell Fate Determination in C. elegans.- 19.3.2 Cytoskeletal Mechanisms Orient the Spindles Precisely in the Determinative Cleavages of the P Lineage.- 19.3.3 Maternal Cytoplasmic Factors Play a Role in the Determination of Cell Fate.- 19.3.4 Most Lineages Are Established by the 51-Cell Stage but Some Cell-Fate Decisions Depend on Early Cell Interactions.- 19.4 Mutational Analysis of Embryogenesis in C. elegans.- 19.4.1 Maternal Gene Products Control and Support Much of Early Embryogenesis.- 19.4.2 Embryonic Gene Activity Plays a Role in Cell-Fate Determination and Morphogenesis.- 19.5 Outlook.- 19.6 Summary.- References.- 20 Generation of Temporal and Cell Lineage Asymmetry During C. elegans Development.- 20.1 Introduction.- 20.2 unc-86 Couples Cell Lineage and Cell Identity.- 20.3 Genetic Analysis of Cell-Cell Signaling During C. elegans Development.- 20.3.1 let-23 Is Necessary for Intercellular Signaling and is a Member of the EGF-Receptor Superfamily.- 20.3.2 let-60 Is Necessary for Intercellular Signaling and Encodes the G elegans ras homolog.- 20.3.3 Other Genes Involved in Intercellular Signaling.- 20.3.4 Summary of Genes Involved in Cell-Cell Signaling.- 20.4 Genetic and Molecular Studies of Heterochronic Genes in C. elegans.- 20.4.1 A Temporal Gradient in the lin-14 Nuclear Protein.- 20.4.2 How Other Heterochronic Genes Interact with lin-14 to Generate the Temporal Gradient or Interpret It.- 20.4.3 Summary: Generation of the lin-14 Temporal Gradient.- 20.5 Outlook.- References.- 21 Genetic and Molecular Analysis of Early Pattern Formation in Drosophila.- 21.1 Drosophila as a Genetic System.- 21.2 Oogenesis and Embryogenesis.- 21.3 Experimental Embryology.- 21.3.1 The Blastoderm Fate Map.- 21.3.2 Systematic Mutagenesis.- 21.4 The Developmental Gene Hierarchy.- 21.4.1 Anterior-Posterior Determination.- 21.4.2 The Dorso-Ventral System.- 21.5 Outlook.- 21.6 Summary.- References.- 22 Generation of Pattern in Drosophila melanogaster Adult Flies.- 22.1 Introduction.- 22.2 Developmental Analysis.- 22.3 Clonal Analysis.- 22.3.1 Developmental Compartments Are Supra-Cellular Units, Polyclonal in Origin.- 22.3.2 The Elements of the Epidermis Develop in Place.- 22.3.3 Size and Shape of Patterns Do Not Result from Mechanisms Which Count Cell Divisions.- 22.3.4 Cell-Cell Interactions Are Involved in Pattern Formation.- 22.4 Genetic and Molecular Analyses.- 22.4.1 Systemic Genes.- 22.4.2 Cell Communication and Proliferation Genes.- 22.4.3 Terminal Differentiation Genes.- 22.5 Comparative Analysis of Patterns.- 22.6 Outlook and Summary.- References.- 23 Genetic Mechanisms in Early Neurogenesis of Drosophila melanogaster.- 23.1 Introduction.- 23.2 The Neuroectoderm Gives Rise to a Constant Array of Neuroblasts.- 23.3 Cellular Interactions Lead to Cell Commitment.- 23.4 Genes Required for Neurogenesis.- 23.5 The Neurogenic Genes Are Functionally Interrelated.- 23.6 NOTCH and DELTA Encode Transmembrane Proteins with Similarity to the Epidermal Growth Factor, EGF.- 23.7 Physical Interactions Between NOTCH and DELTA.- 23.8 The Enhancer of Split Gene Complex [E(SPL)-C] Comprises Several Related Functions.- 23.9 The AS-C Gene, daughterless and the Genes of the [E(SPL)-C] Are Members of the Same Gene Family.- 23.10 The AS-C Genes Are Required for Neuroblast Commitment.- 23.11 Interactions Between Neurogenic and Proneural Genes.- 23.12 Outlook and Summary.- References.- 24 Xenopus Embryogenesis.- 24.1 Introduction.- 24.2 The Oocyte.- 24.2.1 The Xenopus Oocyte as a Test Tube.- 24.2.2 Nucleocytoplasmic Transport of RNA and Proteins.- 24.2.3 Cytoplasmic Localization of mRNA.- 24.3 Egg Maturation and Fertilization.- 24.3.1 Regulation of Translation During Xenopus Oocyte Maturation.- 24.4 Mesoderm Induction.- 24.4.1 Early Molecular Responses to Mesoderm Induction and the Regulation of Muscle Gene Expression.- 24.4.2 Regulatory Elements in Xenopus Muscle Gene Activation.- 24.5 Gastrulation and Neural Inducation.- 24.5.1 Differential Gene Expression in Neural Induction.- 24.6 Analysis of Gene Function in Xenopus Embryogenesis.- 24.6.1 Inhibition of Gene Expression by Antisense RNA/DNA Techniques.- 24.6.2 Embryo Microinjection of Synthetic mRNA.- 24.6.3 Multiple Families of Nucleic Acid Binding Regulatory Proteins.- 24.7 Outlook.- 24.8 Summary.- References.- 25 The Developmental Regulation of the Genes Coding for 5S Ribosomal RNA in Xenopus laevis.- 25.1 Introduction.- 25.2 Ribosome Biogenesis.- 25.3 DNA.- 25.3.1 The 5S RNA Gene Families.- 25.3.2 The 5S RNA Gene.- 25.4 Transcription: the Active State.- 25.4.1 The Transcription Complex.- 25.4.2 Transcription Factor (TF) IIIA.- 25.4.3 Transcription Complex Stability.- 25.5 Regulation - Establishing Differential Transcriptional Activity.- 25.5.1 The in Vivo Regulation of Differential 5S RNA Gene Transcription.- 25.5.2 The Assembly of Chromatin and 5S RNA Gene Transcription.- 25.5.3 A Model for Differential 5S RNA Gene Expression During Early Development.- 25.6 Regulation - Maintaining the Differentiated State.- 25.6.1 Maitenance of Differential Gene Expression.- 25.6.2 Developmental Regulation of TF IIIA Concentration.- 25.6.3 Multiple TF IIIA Protein Variants.- 25.7 Outlook.- 25.8 Summary.- References.- 26 From Drosophila to Mouse.- 26.1 Introduction.- 26.2 Embryogenesis of the Mouse.- 26.3 Developmental Control Genes Derived from Drosophila.- 26.3.1 Homeobox Genes.- 26.3.2 Engrailed-Type Homeobox Genes.- 26.3.3 Paired-Box Genes.- 26.3.4 Finger-Containing Genes.- 26.4 Octamer-Binding Proteins and Genes.- 26.5 The Protein Products as Transcription Factors.- 26.6 Outlook.- 26.7 Summary.- References.- 27 Cloning Developmental Mutants from the Mouse t Complex.- 27.1 Introduction.- 27.1.1 Why Clone Mouse Developmental Mutants?.- 27.1.2 The Mouse t Complex.- 27.1.3 Historical Perspective.- 27.2 Current Understanding of t Complex Genetics.- 27.3 t Complex-Associated Phenomena.- 27.3.1 Interaction with Brachyury (T).- 27.3.2 Embryonic Lethality.- 27.3.3 Male Sterility and Altered Gamete Transmission Ratios.- 27.3.4 Recombination Suppression.- 27.4 Cloning t Complex Developmental Mutants.- 27.4.1 Step 1: Mapping the Mutant Gene with Respect to Falnking Chromosomal Markers.- 27.4.2 Step 2: Cloning the Genomic DNA Containing the Mutant Gene Locus.- 27.4.3 Step 3: Identifying Coding Sequences in Genomic DNA.- 27.4.4 Step 4: Correlation of a Candidate Gene with the Developmental Mutant.- 27.5 Outlook.- 27.6 Summary.- References.- 28 The Use of in Situ Hybridisation to Study the Molecular Genetics of Mouse Development.- 28.1 Introduction.- 28.2 The Technique of in Situ Hybridisation.- 28.3 The Value of Analysing Expression Patterns.- 28.3.1 Correlation of Gene Expression with Developmental Events.- 28.3.2 Conserved and Divergent Expression Patterns in Different Organisms.- 28.3.3 Genetics and Expression Studies Are Powerful in Combination.- 28.3.4 Expression Patterns Can Provide Insight into Developmental Mechanisms.- 28.4 Some Pitfalls in the Interpretation of Expression Patterns.- 28.5 Outlook.- 28.5.1 Technical Advances in in Situ Hybridisation.- 28.5.2 Insights into Gene Function and Mechanisms of Development.- 28.6 Summary.- References.- 29 Insertional Mutagenesis and Mouse Development.- 29.1 Introduction.- 29.2 Mobile Genetic Elements.- 29.3 Endogenous Retroviruses and Insertional Mutagenesis of the Mouse Germ Line.- 29.3.1 Ecotropic Retroviruses and Insertional Mutation of the Dilute Gene.- 29.3.2 Nonecotropic Retroviruses and Insertional Mutation of the Hairless Gene.- 29.3.3 Spontaneous Reintegrations and Insertional Mutations in Hybrid Mouse Strains.- 29.4 Exogenous Retroviruses and Insertional Activation of Oncogenes in Somatic Cells.- 29.4.1 Identification and Isolation of int-1.- 29.4.2 Identification of Other Proto-Oncogenes.- 29.5 Transgenic Mice and Experimentally Induced Insertional Mutations.- 29.5.1 Identifying and Characterizing New Insertional Mutations.- 29.5.2 Isolating Genes Identified by Random Insertion of Injected DNA.- 29.5.3 Isolating Genes Identified by Random Insertion of Exogenous Retroviruses.- 29.5.4 Inducing and Selecting Specific Insertional Mutations.- 29.6 Outlook.- 29.6.1 New Strategies for Random Insertional Mutagenesis in Transgenic Mice.- 29.6.2 Nonrandom Insertional Mutagenesis: Targeting Mutations by Homologous Recombination.- 29.7 Summary.- References.- 30 The Introduction of Genes into Mouse Embryos and Stem Cells.- 30.1 Introduction.- 30.2 Methods for Introducing Genes into Mouse Embryos.- 30.2.1 DNA Injection into Fertilized Eggs.- 30.2.2 Infection of Embryos with Retroviral Vectors.- 30.2.3 Gene Transfer Using Embryonic Stem (ES) Cells.- 30.3 Expression of Introduced Genes in Transgenic Mice.- 30.3.1 To Study Gene Control.- 30.3.2 To Change the Physiology of Mice.- 30.3.3 To Study Oncogene function.- 30.3.4 To Investigate Complex Systems.- 30.4 The ES Cell System.- 30.4.1 The Gain of Function Approach.- 30.4.2 The Loss of Function Approach.- 30.5 Gene Transfer into Hematopoietic Stem Cells.- 30.5.1 The Hematopoietic System.- 30.5.2 Rationale for Retrovirus-Mediated Gene Transfer.- 30.5.3 Protocol for Infection.- 30.5.4 Clonal Analysis of Retrovirus-Transduced Stem Cells.- 30.5.5 Alteration of Hematopoiesis by Retrovirus-Mediated Gene Transfer.- 30.6 Outlook.- 30.7 Summary.- References.- 31 Skeletal Muscle Differentiation.- 31.1 Introduction.- 31.2 Differentiated Skeletal Muscle.- 31.2.1 Physiology and Histology.- 31.2.2 Muscle Diversity and Contractile Protein Isoforms.- 31.2.3 Multigene Families and Alternative RNA Splicing.- 31.2.4 Genetic Studies of Skeletal Muscle Differentiation.- 31.3 Differentiation of Embryonic Skeletal Muscle.- 31.3.1 Transcriptional Regulation During Myoblast Differentiation.- 31.3.2 Identification of Some Myogenic Regulatory Genes: myd and the MyoD Family of Genes.- 31.3.3 Some Properties of MyoD1, myf5, Myogenin, and MRF4 Genes.- 31.4 Embryological Origins of Skeletal Muscle.- 31.4.1 Somite Origins of Vertebrate Muscle.- 31.4.2 Determination of Myoblasts: Role of Cell-Cell Interaction.- 31.4.3 Expression of MyoD in Invertebrates.- 31.5 Outlook.- 31.6 Summary.- References.- 32 Hepatocyte Differentiation.- 32.1 Introduction.- 32.2 Embryologic Origin of the Liver.- 32.3 Cell Lineages in the Embryonic Liver.- 32.4 Environment Versus Autonomy in Hepatocyte Differentiation.- 32.5 Cell-Autonomous Genetic Cascades in Hepatocyte Differentiation.- 32.5.1 Hepatocyte Nuclear Factor-1?.- 32.5.2 Hepatocyte Nuclear Factor-1? (HNF-1?, also vHNF, vAPF).- 32.5.3 CAAT/Enhancer Binding Protein.- 32.5.4 DBP and LAP, Related Members of the C/EBP Family.- 32.5.5 Hepatocyte Nuclear Factov-3??? (HNF-3???).- 32.5.6 Hepatocyte Nuclear Factor-4 (HNF-4).- 32.5.7 Combinatorial Models of Liver Determination.- 32.5.8 Combinatorial Models of Transcription Factor Action.- 32.5.9 Multi-Tiered Regulation of Liver Transcription Factors.- 32.6 Environmental Influences on Hepatocyte Differentiation.- 32.6.1 Circulating Differentiation Factors.- 32.6.2 Cell-Cell Interactions.- 32.6.3 Cell-Matrix Interactions.- 32.7 Outlook.- 32.8 Summary.- References.- 33 Cellular Differentiation in the Hematopoietic System: an Introduction.- 33.1 A Brief Description of the Cells and Their Functions.- 33.1.1 Hematopoietic Stem Cells.- 33.1.2 Progenitor Cells.- 33.1.3 Morphologically Identifiable Immature Cells or Precursors.- 33.2 Stochastic Versus Deterministic Mechanisms in the Commitment to Individual Hematopoietic Lineages.- 33.3 Growth Factors in Hematopoiesis.- 33.4 Cell-Cell Contacts in Hematopoiesis.- References.- 34 The Role of Oncogenes in Myeloid Differentiation.- 34.1 Introduction.- 34.1.1 The Normal Myeloid Pathway of Differentiation.- 34.1.2 The Transformed Myeloid Cells to Study Differentiation.- 34.1.3 The Cell Lines as Models to Study Differentiation.- 34.1.4 Retroviruses and Oncogenes.- 34.2 The Role of Oncogenes in Myeloid Differentiation.- 34.2.1 The Avian Defective Retroviruses Which Cause Acute Myeloid Leukemias.- 34.2.2 The Murine Acute Retroviruses Which Transform Myeloid Cells.- 34.2.3 The Murine Chronic Retroviruses that Cause Myeloid Leukemias.- 34.2.4 Potential Oncogenes in Human Myeloid Leukemias.- 34.3 The Role of Proto-Oncogenes in Myeloid Differentiation.- 34.3.1 Studies in Normal Cells.- 34.3.2 Studies of Differentiating Cell Lines.- 34.4. Transgenic Mice.- 34.5 Outlook and Summary.- References.- 35 Developmental Regulation of Human Globin Genes: a Model for Cell Differentiation in the Hematopoietic System.- 35.1 Introduction.- 35.2 The Human Globin Genes: a Paradigm for Cell Type-Specific Gene Expression in the Erythroid Lineage.- 35.2.1 Distant DNA Sequences 5? to the Globin Gene Clusters Regulate the Expression of All Globin Genes.- 35.2.2 Deletions Causing ?- ?- ?-Thalassemia May Remove a Region Controlling Globin Gene Expression.- 35.2.3 The Locus Control Region (LCR) Allows High-Level, Erythroid-Specific, Position-Independent Gene Expression.- 35.2.4 Crucial Elements of the LCR Are Marked by DNase Hypersensitive Sites (HS Sites).- 35.2.5 LCR Activity May Be Mediated by Long-Range Effects on Chromatin Structure.- 35.2.6 Individual HS Sites Are Sufficient for Position-Independent High-Level-Expression.- 35.3 Erythroid and Stage-Specific Elements Mediating Expression of Individual Globin Genes.- 35.3.1 The Hemoglobin Pattern Is Modulated Throughout the Whole Development Within a Single Cell Population.- 35.3.2 Inherited Defects of the Regulation of Fetal Hemoglobin Synthesis in Humans (Hereditary Persistence of Fetal Hemoglobin, HPFH) Provide Clues to the Identification of Regulatory Elements.- 35.3.3 Transgenic Mice. Globin Gene Regulatory Elements Are Located Both 5?, Within, and 3? to the Genes.- 35.3.4 In Transgenic Mice the LCR Linked to Individual Globin Genes Overrides Their Stage-Specific Regulation.- 35.3.5 Binding Sites for the Same Erythroid-Specific and Ubiquitous Factors Are Present in the Globin Promoter, Enhancer, and LCR Regions.- 35.3.6 GATA-1 and NFE-2 Binding Sites Are Present in Several Erythroid-Specific Genes.- 35.3.7 Elements Regulating Globin Gene Expression Are Conserved in Evolution.- 35.4 Several Hematopoietic Cell Types Express GATA-1.- 35.4.1 Genes Expressed in Megakaryocytes Bind to and Are Regulated by GATA-1.- 35.4.2 The Gene Encoding GATA-1 May Be Activated in a Common Progenitor of Several Lineages.- 35.4.3 GATA-1 Is Necessary, but not Sufficient, for Erythroid Differentiation.- 35.4.4 The Same Transcription Factors Coordinately Regulate Genes Which Are Involved in Several Aspects of Cell Differentiation as Well as Proliferation.- 35.4.5 Which Mechanisms Are Responsible for Establishing the Cell-Specific Pattern of Expression of Transcription Factors?.- 35.5 Growth Factors Are Involved in the Differentiation of Hematopoietic Cells.- 35.5.1 Transfection into Hematopoietic Cells of Genes Encoding Growth Factor Receptors May Stimulate Proliferation and Allow Survival.- 35.5.2 Growth Factors May Cause Differentiation.- 35.6 A Complex Network of Interactions at Several Distinct Levels Underlies Terminal Differentiation.- 35.7 Summary and Outlook.- References.- 36 Growth Control in Animal Cells.- 36.1 Introduction.- 36.2 The Cell Cycle.- 36.3 Controls in the Cell Cycle.- 36.4 Cell-to-Cell Signaling.- 36.5 Growth Stimulatory Factors.- 36.6 Growth Factors and Cell Multiplication.- 36.7 Growth Factors and Transformation.- 36.8 Growth Factor Receptors.- 36.9 The Intracellular Signal Pathway.- 36.10 Oncogenes in the Signal Pathway.- 36.11 Nuclear Response Elements.- 36.12 Cell Cycle-Regulated Genes.- 36.13 Gene Expression at Quiescence.- 36.14 Growth Inhibitory Factors.- 36.14.1 Interferons (IFNs).- 36.14.2 Transforming Growth Factor Beta (TGF?).- 36.15 Control of Growth Arrest.- 36.15.1 Tumor Suppressor Genes.- 36.16 Outlook.- 36.17 Summary.- References.