Cell Differentiation

Three years have elapsed since the publication of the first edition of this book (in German). The continued interest of our readers and the rapid progress of our knowl­ edge in many fields necessitates a thoroughly revised and somewhat enlarged new edition. Cell differentiation is a prerequisite of life. It is defined as the prooess leading to the qualitatively and quantitatively selective realization of distinct parts of a given genetic material. Cell differentiation comprises five main aspects: (1) signal reception and transformation, (2) selective rearrangements of the genetic material, (3) differen­ tial gene expression, (4) organization of gene expression programs and (5) intercellular coordination of cell differentiation within the developmental programs of multicellular organisms. Despite the bewildering multiplicity of its results, i.e., the differentiated phenotypes of cells, there are apparently fundamental similarities with respect to the molecular mechanisms of the process itself. These mechanisms constitute the central subject of this book.

Introductory Part.- 1. Biochemistry of Gene Expression.- 1.1 Introduction: Biological Information.- 1.2 The Genetic Material.- 1.2.1 Structure of DNA.- 1.2.2 Organisation of Bacterial Chromosomes.- 1.2.3 Organisation of the Genetic Material in Eukaryotic Cells.- 1.2.3.1 DNA Sequence Classes.- 1.2.3.2 Basic Proteins Associated with DNA.- 1.2.3.3 Non-Histone Chromosomal Proteins.- 1.2.3.4 Organizational Levels of Chromatin.- 1.3 Realization of the Genetic Information.- 1.3.1 The Genetic Code.- 1.3.2 Transcription.- 1.3.2.1 RNA-Polymerases in Prokaryotic and Eukaryotic Cells.- 1.3.2.2 The Transcription Cycle.- 1.3.2.3 Initiation and Termination Sequences for Transscription.- 1.3.3 Transcription Products and RNA Processing.- 1.3.3.1 Pre-mRNA Processing.- 1.3.3.2 Processing of rRNA and tRNA Precursors.- 1.3.4 Translation.- 1.3.4.1 tRNA Structure and Function.- 1.3.4.2 Structure and Function of Ribosomes.- 1.3.4.3 The Translation Cycle.- 1.3.5 Proteinogen Processing.- 1.3.6 Protein Degradation.- 1.4 Selected References.- 2. Restriction Enzymes and Techniques for Gene Analysis and Synthesis.- 2.1 Introduction.- 2.2 Restriction Endonucleases.- 2.3 Cloning of DNA Fragments and Generation of Clone Libraries.- 2.4 Cloning Vectors.- 2.5 In vitro Packaging of ? DNA.- 2.6 Detection of DNA Fragments by Hybridization Techniques.- 2.7 In vitro Labelling of DNA Fragments.- 2.8 Functional Characterization of mRNA and DNA Fragments in Xenopus Oocytes and in the HART Assay.- 2.9 DNA Restriction Mapping.- 2.10 DNA Sequencing.- 2.11 Gene Synthesis.- 2.12 Conclusions.- 2.13 Selected References.- General Part.- 3. “Sonderung”, Differentiation, Cell Differentiation — a Sketch of the History of Concepts.- 3.1 New Methods — New Conceptions.- 3.2 Etymology.- 3.3 Landmarks in the History of Developmental Biology.- 3.3.1 Comparative Developmental Biology.- 3.3.2 The Causal Phase of Developmental Biology.- 3.3.3 Molecular Developmental Biology.- 3.4 Selected References.- 4. Molecular Basis of Cell Differentiation.- 4.1 Cell Differentiation as a Prerequisite of Life.- 4.1.1 Definitions.- 4.1.2 Determination and Irreversibility of Cell Differentiation.- 4.1.3 Proteins and RNA’s as Primary Products of Cell Differentiation.- 4.1.4 Compartmentation of Gene Expression.- 4.1.5 Two Types of Regulatory Information.- 4.1.6 Five Main Aspects of Cell Differentiation.- 4.2 Signal Reception and Transformation.- 4.2.1 Classification of Signal Systems.- 4.2.2 Group I: Nutrient Signal Systems.- 4.2.2.1 Receptor-Mediated Endocytosis and Regulation of Cholesterol Homeostasis in Animal Cells.- 4.2.3 Group II: Metabolic Integrator Systems of Bacteria.- 4.2.3.1 C-Catabolite Repression.- 4.2.3.2 Signal Transformation by the Glutamine Synthetase System.- 4.2.4 Group III: Hormonal Signal Systems.- 4.2.4.1 Model of the Membrane-Bound Hormone Receptors and the Role of Adenylate Cyclase in Animal Cells.- 4.2.4.2 Gonadotropin Control of Steroidogenesis.- 4.2.4.3 Evidence for the Floating Receptor Model.- 4.3 Selective Genome Rearrangements.- 4.3.1 Transposable Elements in Bacteria.- 4.3.2 Phase Variation in Salmonella.- 4.3.3 Switch of Mating Type in the Yeast Saccharomyces cerevisiae.- 4.3.4 Middle Repetitive Sequences of Eukaryotic Chromatin Contain Transposable Elements.- 4.3.5 Transposable Control Element Systems in Maize.- 4.4 Differential Gene Expression.- 4.4.1 Gene Expression: Partial Processes and Amplification of Information.- 4.4.2 Gene Activation and Transcription.- 4.4.2.1 Transcription Units in Bacteria.- 4.4.2.2 The Regulatory Region of the lac Operon in Escherichia coli.- 4.4.2.3 Promoter Strength — An Element of Specific Transcriptional Control.- 4.4.2.4 Morphology of Transcriptionally Active Genes in Prokaryotic and Eukaryotic Cells.- 4.4.2.5 Structure and Function of Eukaryotic Genetic Systems.- 4.4.2.5.1 Regulatory Elements of the ?-Glucuronidase Gene Complex of Mouse.- 4.4.2.5.2 The Human Globin Gene System.- 4.4.2.5.3 Elements of Higher Order Chromatin Structure as Related to Determination and Differential Gene Activity.- 4.4.2.5.4 Conclusion: Properties of Activated vs. Non-Activated Chromatin.- 4.4.2.6 Transcription Specificity of RNA Polymerase Isozymes.- 4.4.2.7 Termination and Antitermination.- 4.4.3 Control of Pre-mRNA Processing and mRNA Degradation.- 4.4.3.1 Pre-mRNA Processing: Nuclear Organization and Selective Information Transfer.- 4.4.3.2 Role of Guide RNA’s.- 4.4.3.3 Inactivation and Degradation of mRNA.- 4.4.4 Translation Regulation.- 4.4.4.1 Elements of mRNA Secondary Structure.- 4.4.4.2 Inactivation of the Cap-Binding Factor after Virus Infection.- 4.4.4.3 The Translation Program of Escherichia coli RNA Phages MS2 and Q?.- 4.4.4.4 Functional Compartmentation of Cytoplasmic mRNP in Eukaryotes.- 4.4.4.5 Hemin-Controlled Translation Inhibition in Reticulocytes.- 4.4.4.6 Functional Adaptation of the tRNA Pattern.- 4.4.4.7 Translational Control in Interferon Treated Mammalian Cells.- 4.4.5 Proteinogen Processing.- 4.4.5.1 Proteinogen Processing — an Essential Means to Guide Proteins to Their Proper Compartments.- 4.4.5.1.1 The Signal Hypothesis.- 4.4.5.1.2 Synthesis of Membrane Proteins.- 4.4.5.1.3 Cytoplasmic Synthesis of Organellar Proteins.- 4.4.5.2 Proteinogen Processing Determines Local Deposition of Chitin in Budding Yeast.- 4.4.5.3 Proteinogen Processing in the Propagation Cycle of Animal Viruses.- 4.4.6 Biological Inactivation and Degradation of Proteins.- 4.5 Gene Expression Programs.- 4.5.1 Mechanisms for Coordination of Gene Expression Programs.- 4.5.2 Sequential Enzyme Induction.- 4.5.3 Bacterial Sporulatio n.- 4.5.4 Programmed Gene Expression During Erythroid Cell Specialization in Mammals.- 4.5.4.1 Hemopoietic Stem Cells and Erythroid Homeostasis.- 4.5.4.2 Friend Erythroleuketnia Cells as Models of Red Cell Maturation.- 4.5.4.3 Regulation of Globin Synthesis and the Molecular Pathology of Thalassemia Syndromes.- 4.5.4.4 “Suicide” Maturation in the Erythroid Lineage.- 4.6 Cell Differentiation and Development.- 4.6.1 Intercellular Signals Controlling the Developmental Cycle of Myxobacteria.- 4.6.2 Mechanisms of Cell Sorting and Positioning in Mammals.- 4.6.3 Morphogen Gradients Control Pattern Formation During Early Developmental Stages of Drosophila.- 4.6.4 Role of Intercellular Signals for the Development and Function of the Sexual System in Mammals.- 4.6.4.1 Development of the Sexual System.- 4.6.4.2 Germ Cell Differentiation.- 4.7 Conclusions.- 4.8 Selected References.- Special Part.- 5. Regulation of Adaptive Enzyme Synthesis in Prokaryotes Exemplified by the Arabinose Regulon of Escherichia coli.- 5.1 Biochemistry, Enzymatics and Genetics of the Arabinose Degradation.- 5.2 Genetic Investigations on the Control of Gene Expression in the ara BAD Operon.- 5.2.1 The Regulatory Gene ara C.- 5.2.2 The Operator-Initiator Region, ara OI.- 5.3 Catabolite Repression in the ara Regulon.- 5.4 Regulation of ara C Gene Expression.- 5.5 In Vitro Investigations to Characterize the Regulatory Mechanisms in the ara BAD Operon.- 5.5.1 Enrichment and Isolation of Genes of the ara CBAD Region.- 5.5.2 Purification and Characterization of the ara C Protein.- 5.5.3 Evidence of the Regulation Level.- 5.5.4 In Vitro Transcription and Translation of the ara CBA Genes.- 5.5.5 Electron Microscopic Localisation of the Transcription-Initiation Complex.- 5.5.6 Assay of the Codogen Strand for the ara BAD and ara C operons.- 5.6 Conclusions: Regulatory Interactions in the ara OI Region as a Model of a Complex Transcription Control.- 5.7 Selected References.- 6. Light-induced Chloroplast Differentiation.- 6.1 Structure and Function of Chloroplasts.- 6.2 The Genetic Aspect of Chloroplastogenesis.- 6.2.1 Molecular Organization of Chloroplast DNA.- 6.2.2 Sites of Coding and Synthesis of Plastid Proteins.- 6.3 Light-Induction of Plastid Differentiation.- 6.3.1 Proplastids and Etioplasts.- 6.3.2 Photoreceptors.- 6.3.3 Phases of Chloroplast Formation.- 6.4 Selected Examples of Gene Expression During Chloroplast Differentiation.- 6.4.1 Ribonucleic Acids.- 6.4.2 Ribulose-1,5-Bisphosphate Carboxylase.- 6.4.3 Leucyl-tRNA Synthetase.- 6.4.4 Thylakoid Membrane Constituents.- 6.5 Regulatory Aspects in Chloroplastogenesis.- 6.5.1 Hypothetic “Repressors” and “Derepressors”.- 6.5.2 Role of Mitochondria During Chloroplast Formation.- 6.6 Selected References.- 7. The Action of Estrogen on Gene Expression in Chick Oviduct.- 7.1 Regulation of Estrogen Biosynthesis and Estrogen Level.- 7.2 Cell Specialization Induced by Estrogen Action in Chick Oviduct.- 7.3 Structural Basis of Synthesis and Release of Ovalbumin.- 7.3.1 Organization of the Ovalbumin Gene.- 7.3.2 Structure of Ovalbumin mRNA.- 7.3.3 Translocation of Ovalbumin Through the Membrane of the Rough ER.- 7.4 Control of mRNA Transcription by Estradiol.- 7.4.1 Binding of Estradiol to Hormone Receptors.- 7.4.2 Interaction of Steroid Hormone-Receptor Complexes with Chromatin.- 7.4.3 Influence of Estradiol on RNA Polymerase Initiation Sites.- 7.4.4 Influence of Estrogen on the Transcription of the Ovalbumin Gene.- 7.4.5 Role of Non-Histone Proteins of Chromatin on Transcription of Ovalbumin-specific RNA.- 7.5 Conclusions.- 7.6 Selected References.- 8. Insulin-Biosynthesis and Mode of Action.- 8.1 Introduction: Scientific History of Insulin.- 8.2 Molecular Pathology of Diabetes mellitus.- 8.3 Development of the Endocrine Pancreas.- 8.3.1 Cell Types in the Islets of Langerhans.- 8.3.2 Differentiation of the Islet Cells.- 8.3.3 Proliferation and Neogenesis of Islet Cells.- 8.4 Mechanism of Insulin Biosynthesis.- 8.4.1 Intracellular Organization of Insulin Biosynthesis.- 8.3.2 Fine Structure of Insulin Genes.- 8.4.3 mRNA and Regulation of Transcription.- 8.4.4 Insulin is Synthesized as a Pre-Prohormone.- 8.4.5 Proinsulin, Proinsulin Processing and Insulin Degradation.- 8.4.6 Mechanism of Insulin Secretion.- 8.5 Paracrine or Endocrine Relations Between Different Cell Types of the Islets of Langerhans?.- 8.5.1 Biosynthesis of Glucagon and Somatostatin.- 8.5.2 Mechanisms of Cell-Cell Interaction in the Islets of Langerhans.- 8.6 Mechanisms of Insulin Action.- 8.6.1 Metabolic Alterations in the Target Cells.- 8.6.2 Signal Transformation and Hormone Action.- 8.6.2.1 Insulin Binding to the Membrane Receptor.- 8.6.2.2 Internalization of the Hormone-Receptor Complex.- 8.6.2.3 Intracellular Redistribution and Degradation of Insulin.- 8.6.2.4 Antireceptor Antibodies Mimic Insulin Effects.- 8.7 Conclusions.- 8.8 Selected References.- 9. Polytene Chromosomes — Model Objects for Studying Differential Gene Activities in Specialized Cells.- 9.1 Structure of Dipteran Polytene Chromosomes.- 9.1.1 Studies Employing Light and Electron Microscopy.- 9.1.2 DNA of Polytene Chromosomes.- 9.1.2.1 DNA Content of Chromorneres.- 9.1.2.2 Polytenization and DNA Replication.- 9.1.3 Proteins Associated with Polytene Chromosomes.- 9.2 The Puffing Phenomenon.- 9.2.1 Puffs as a Manifestation of Transcription Activity.- 9.2.1.1 Puffs and RNA Synthesis.- 9.2.1.2 Puffing Leads to Characteristic Changes of Chromomere Structure.- 9.2.2 Puff Patterns as Indicators of the Gene Expression Program in Polytene Tissues.- 9.2.2.1 Development and Tissue Specificity of Puffing.- 9.2.2.2 Hormones as Inductors of Specific Changes of Puff Patterns.- 9.2.2.3 Puff Induction and Repression by Heat-Shock.- 9.3 Molecular Basis of Gene Expression of Puff DNA.- 9.3.1 Synthesis and Processing of High Molecular Weight Puff RNA of Chironomus.- 9.3.2 The Heat-Shock Gene Expression Program of Drosophila melanogaster.- 9.4 High Molecular Weight Structural Proteins of Insects are Coded by Internal Repetitive Genes: A Comparison of Balbiani Ring and Fibroin Genes.- 9.4.1 Balbiani Ring Genes of Chironomus.- 9.4.1.1 Balbiani Rings and the Synthesis of Secretory Proteins.- 9.4.1.2 Synthesis of High Molecular Weight Balbiani Ring RNA.- 9.4.1.3 Molecular Characterization of BR-RNA and BR-DNA.- 9.4.1.4 Nucleo-Cytoplasmic Transport of BR-RNA.- 9.4.2 Structure and Expression of the Fibroin Gene in Silk Glands of Bombyx mori Larvae.- 9.5 Conclusions.- 9.6 Selected References.- 10. Expression of Isozymes and Their Function in Differentiation.- 10.1 Introduction.- 10.2 Isozymes in Amino Acid Metabolism of Enterobacteria.- 10.2.1 Bacterial Isozymes Involved in Metabolic Channeling.- 10.2.2 Biosynthetic and Degradative Processes Initiated by Alternative Isozymes.- 10.2.3 Biosynthetic Threonine Deaminase and the ilv Regulon.- 10.2.3.1 Multivalent Repression of Biosynthetic Threonine Deaminase.- 10.2.3.2 Biosynthetic Threonine Deaminase as Part of a Complex Gene Control System.- 10.2.3 Biodegradative Threonine Deaminase: Multivalent Induction and Role of cAMP.- 10.3 Isozymes of Eukaryotic Cells.- 10.3.1 Isozymes Are Involved in Most Steps of Sugar Metabolism in Vertebrates.- 10.3.2 Three Functionally Distinct Pyruvate Kinase Isozymes in Mammals.- 10.3.3 Mammalian Signal Transformation: Involvement of Protein Kinases and Other Isozyme Systems.- 10.3.3.1 The Concept of Signal Transformation.- 10.3.3.2 Role of Adenylate Cyclase.- 10.3.3.3 Protein Kinase Isozymes.- 10.3.3.4 All Steps Involved in Signal Transformation Are Reversible.- 10.3.3.5 Isozymes Involved in Signal Transformation Are Modulated by Protein Factors and Enzymes.- 10.3.3.6 Recompartmentation of Protein Kinase Isozymes.- 10.3.3.7 Phosphorylation of Nuclear Proteins.- 10.3.3.7.1 Phosphorylation of Nuclear Proteins Triggered by cAMP.- 10.3.3.7.2 Specialized Protein Kinases Encoded by Vertebrate Tumor Viruses.- 10.3.3.7.3 Phosphorylation of Certain Non-Histone Proteins Directly Affects Transcription.- 10.3.3.8 Competence and Compartmentation of Cells Provide the Basis for Specific Action of Multifunctional Protein Kinases.- 10.4 Conclusions.- 10.5 Selected References.- 11. The Expression of Secondary Metabolism — an Aspect of Cell Specialization.- 11.1 What is Secondary Metabolism?.- 11.2 Phase-Dependent Formation of Enzymes of Secondary Metabolism.- 11.2.1 The Role of Light in Triggering Formation of Enzymes Involved in Flavonoid Metabolism in Parsley Cell Cultures.- 11.2.2 Induction of Phenylalanine Ammonia-Lyase and Flavanone Synthase in Parsley Cell Cultures.- 11.3 Integration of Secondary Metabolism in the Program of Cell Specialization and Development.- 11.3.1 Expression of Alkaloid Synthesis during Chemical Specialization of Hyphal Cells of the Mould Penicillium cyclopium.- 11.3.2 Alkaloid Metabolism During the Formation of Conidiospores.- 11.4 Influence of Signals on the Expression of Alkaloid Metabolism.- 11.5 Alkaloid Metabolism in Mutants with Modified Developmental Programs.- 11.6 Conclusions.- 11.7 Selected References.- 12. Biosynthesis and Accumulation of Storage Proteins in Developing Plant Seeds.- 12.1 Stages of Seed Development.- 12.1.1 Growth Characters of Seeds.- 12.1.2 Cytological Characters of Seed Development.- 12.1.3 DNA Accumulation.- 12.1.4 Accumulation of RNA and Ribosomes.- 12.1.5 Protein Accumulation.- 12.1.5.1 Biochemical Characters of Storage Proteins.- 12.1.5.2 Accumulation of Storage Proteins During Seed Development.- 12.2 Regulation of Storage Protein Biosynthesis.- 12.2.1 Endoreduplication of DNA.- 12.2.2 Evidence for Transcriptional Control of the Formation of Storage Proteins.- 12.2.3 Molecular Cloning of cDNA Copies of Storage Protein mRNA and Gene Analysis.- 12.2.4 Control of Translation and Processing of Polypeptide Precursors of Storage Proteins.- 12.3 Biogenesis of Protein Bodies and the Storage of Protein Reserves.- 12.4 Conclusions.- 12.5 Selected References.- 13. Determination and Function of the Immune System.- 13.1 Introduction.- 13.1.1 The Immune System.- 13.1.2 Structure and Heterogeneity of Immunoglobulins.- 13.2 Determination and Maturation of Immune Competent Cells.- 13.2.1 Phases of Cell Specialization and the Origin of Antibody Diversity.- 13.2.2 Structure and Rearrangements of Immunoglobulin Genes.- 13.2.2.1 Fusion of V- and C-Gene Segments.- 13.2.2.2 Heavy Chain Switch.-...