ISBN: 3-540-62754-5
TITLE: Development
AUTHOR: Russo, V.E.A.; Cove, D.J.; Edgar, L.G.; Jaenisch, R.; Salamini, F. (Eds.)
TOC:

Section 1 Microbial Systems, Both Prokaryote and Eukaryote 
1 Virus Assembly and Morphogenesis 
Peter Stockley and Nicola Stonehouse 3 
2 Spatial and Temporal Control of Gene Expression in Prokaryotes 
Adam Driks 21 
3 Multicellular Development in the Myxobacteria Myxococcus xanthus 
and Stigmatella aurantiaca 
Eugene W. Crawford Jr. and Lawrence J. Shimkets 35 
4 Cell Type Determination in Yeast 
Xin Bi and James R. Broach 49 
5 Genetic and Environmental Influence on Development 
of the Filamentous Fungus Neurospora crassa 
Oded Yarden and Vincenzo E. A. Russo 67 
6 Cell-Cell Communication in Dictyostelium 
Pauline Schaap and Jeffrey Williams 83 
7 The Cell Division Cycle in Aspergillus nidulans 
John Doonan 99 
Section 2 Plants 
8 Flowering Plant Embryogenesis 
Casper Vroemen and Sacco De Vries 121 
9 Root Development in Arabidopsis 
Liam Dolan 133 
10 Leaf Development 
Carlo Pozzi, Kai J. Mller, Wolfgang Rohde, 
and Francesco Salamini 145 
11 Floral Development: Genetic Views and Molecular News 
Brendan Davies, Hans Sommer, and Zsuzsanna Schwarz-Sommer 167 
12 Genetic Control of Endosperm Development 
Stephen Slocombe, Monika Maitz, Gregorio Hueros, 
Heinz-Albert Becker, Guo Yan, Martin Mller, Serena Varotto, 
Geraldina Santandrea, and Richard D. Thompson 185 
13 Environmental Light Signals and the Development of Arabidopsis 
Giorgio Morelli and Ida Ruberti 199 
14 Plant-Microorganism Symbiosis 
J. Allan Downie and Nicholas J. Brewin 211 
Section 3 Animals 
15 Caenorhabditis elegans: Embryonic Axis Formation; Signalling 
in Early Development 
Craig P. Hunter 233 
16 Cell Fate Determination in Caenorhabditis elegans 
Michael Krause 251 
17 Morphogenesis and Organogenesis in Caenorhabditis elegans 
Lois G. Edgar 269 
18 The Regulation of Cell and Growth Cone Migrations During 
the Development of Caenorhabditis elegans 
William G. Wadsworth 299 
19 Formation of Embryonic Axes and Blastoderm Pattern in Drosophila 
Martin Klingler and Diethard Tautz 311 
20 Early Neurogenesis in Drosophila 
Jos A. Campos-Ortega 331 
21 Drosophila: Imaginal Disk Development: Patterning the Adult Fly 
Seth S. Blair 347 
22 Insertional Mutagenesis in Zebrafish 
Adam Amsterdam and Nancy Hopkins 371 
23 Spatial and Temporal Control of Maternal Message Utilization 
Davor Solter and Barbara B. Knowles 389 
24 DNA Methylation 
Peter W. Laird 395 
25 X-Chromosome Inactivation 
Jeannie T. Lee 407 
26 Genomic Imprinting: Its Role in Development and Disease 
Johanna A. Joyce and Anne C. Ferguson-Smith 421 
27 Myogenesis 
Michael A. Rudnicki 435 
28 Neurotrophins in Development of the Nervous System 
Ernest Arenas and Patrik Ernfors 447 
29 Olfactory Receptor Gene Regulation 
Andrew Chess 463 
30 Genetically Modified Mice as Tools for Cancer Research 
Erwin F. Wagner and Zhao-Qi Wang 471 
31 Circadian Timing in Animals 
Ueli Schibler and Daniel J. Lavery 487 
32 Polarity in Biological Systems 
David J. Cove, Ian A. Hope, and Ralph S. Quatrano 507 
Glossary 525 
Subject Index 537 

Section 1 Microbial Systems, Both Prokaryote and Eukaryote 
1 Virus Assembly and Morphogenesis 
Peter G. Stockley and Nicola J. Stonehouse 3 
1.1 Introduction 3 
1.1.1 Viruses as Model Systems for Development 3 
1.1.2 Self-Assembling Systems: Molecular Ontogeny? 3 
1.1.3 General Principles of Virus Organization 4 
1.2 Molecular Mechanisms of Viral Assembly 6 
1.2.1 Tobacco Mosaic Virus, a Helical Rod 8 
1.2.2 Simple Viral Shells Based on Icosahedral Symmetry 9 
1.2.3 T4 and phi29 Bacteriophages, Examples of Complex Viruses 14 
1.3 Evolutionary Considerations 18 
1.4 Outlook 19 
1.5 Summary 19 
References 20 
2 Spatial and Temporal Control of Gene Expression in Prokaryotes 
Adam Driks 21 
2.1 Introduction 21 
2.2 Temporal Control of Flagellar Gene Expression and 
Spatial Control of the Cell Cycle in C. crescentus 23 
2.2.1 Polar Structures in C. crescentus: the Flagellum 23 
2.2.2 The Hierarchical Organization of the Flagellar Genes 24 
2.2.3 Morphological Coupling of Gene Expression and 
Flagellar Assembly 25 
2.2.4 Cell-Cycle Control 26 
2.3 Temporal Control of Gene Expression During Spore Formation 
in B. subtilis 27 
2.3.1 Spore Formation by B. subtilis 27 
2.3.2 Early Gene Regulatory Events in Sporulation 27 
2.3.3 The Forespore Genetic Program 28 
2.3.4 The Mother Cell Genetic Program 28 
2.4 Spatial Control of Gene Expression During Spore Formation 
in B. subtilis 29 
2.4.1 The Restriction of rho^F Activity to the Forespore 29 
2.4.2 The Activation of Mother Cell Gene Expression by Events 
in the Forespore 30 
2.4.3 Postengulfment Signal Transduction Between Compartments 30 
2.5 Themes in Temporal and Spatial Control: Sequential Activation 
of Genes and Morphogenetic Coupling 31 
2.6 Outlook 31 
2.7 Summary 32 
References 32 
3 Multicellular Development in the Myxobacteria 
Myxococcus xanthus and Stigmatella aurantiaca 
Eugene W. Crawford Jr. and Lawrence J. Shimkets 35 
3.1 Introduction 35 
3.2 The Developmental Program of Myxococcus xanthus 35 
3.2.1 Rippling 36 
3.2.2 Aggregation and Fruiting Body Formation 37 
3.2.3 Sporulation 40 
3.3 The Fundamental Choice to Grow or Develop 40 
3.3.1 The Cellular Starvation Pathway 41 
3.3.2 The Population Starvation Pathway 41 
3.3.3 Arrest of Growth 42 
3.4 Development in Stigmatella aurantiaca 43 
3.4.1 Fruiting Body Formation in Stigmatella aurantiaca 43 
3.4.2 Uncoupling Sporulation and Fruiting Body Formation 44 
3.4.3 Pheromone Production by S. aurantiaca 44 
3.5 Outlook 45 
3.6 Summary 45 
References 45 
4 Cell Type Determination in Yeast 
Xin Bi and James R. Broach 49 
4.1 Introduction 49 
4.2 Phenotypic, Genetic and Molecular Basis 
of Different Cell Types 52 
4.2.1 Mating Factors and Their Receptors 52 
4.2.2 Regulatory Circuitry for Control of Cell Type 53 
4.2.3 Diploids: Sporulation and Pseudohyphal Growth 54 
4.3 Cell Type Switching 55 
4.3.1 HO Regulatory Elements 56 
4.3.2 Cell Cycle Regulation of HO 56 
4.3.3 Mother-Daughter Regulation of HO 57 
4.3.3.1 Asymmetric Localization of ASH1 mRNA 58 
4.3.3.2 Asymmetric Distribution of Ash 1p Depends 
on the Actin Cytoskeleton 58 
4.3.4 Donor Preference in Mating Type Switching 59 
4.3.4.1 A cis-Acting Elements Governs Donor Preference 59 
4.3.4.2 trans-Acting Factors Involved in Donor Preference 61 
4.3.4.3 Mechanism of Donor Preference 62 
4.3.5 Transcriptional Silencing 62 
4.4 Outlook 64 
4.5 Summary 64 
References 64 
5 Genetic and Environmental Influence on Development 
of the Filamentous Fungus Neurospora crassa 
Oded Yarden and Vincenzo E.A. Russo 67 
5.1 Introduction 67 
5.2 Neurospora crassa as a Model for Filamentous Fungi 67 
5.2.1 The Life Cycle of Neurospora crassa 68 
5.2.2 Microbiological and Genetic Techniques 69 
5.3 Morphological Studies 70 
5.3.1 From Spore to Mycelium 70 
5.3.2 From Mycelium to Conidia 70 
5.3.3 The Sexual Cycle 72 
5.4 Genetic Influence on Development 74 
5.4.1 Developmental Genes of Neurospora 74 
5.4.2 Gene Regulation During Conidiation 75 
5.4.3 Protein Phosphorylation in Developmental Processes 75 
5.5 Epigenetic Regulation of Fungal Gene Expression 76 
5.6 Environmental Influence on Development 77 
5.6.1 Nutrient Source 78 
5.6.2 Temperature 78 
5.6.3 Light 78 
5.7 Outlook 79 
5.8 Summary 80 
References 80 
6 Cell-Cell Communication in Dictyostelium 
Pauline Schaap and Jeffrey Williams 83 
6.1 Introduction 83 
6.1.1 Characteristics of the Growing Cell and of Stalk 
and Spore Cells 83 
6.1.2 Outline of the Developmental Cycle 84 
6.2 The Signals that Initiate and Direct Aggregation 86 
6.2.1 Preparing for Development: Cell Density Signalling 86 
6.2.2 The Generation of Oscillatory cAMP Signals 87 
6.2.3 Cellular Responses to cAMP Signals 88 
6.3 Signals that Direct and Pattern Formation 90 
6.3.1 cAMP Signalling and Cell Movement Within the Slug 90 
6.3.2 cAMP and Prespore Differentiation 90 
6.3.3 DIF and Prestalk Differentiation 91 
6.3.4 Cross-Talk Between the DIF and cAMP Signalling Pathways 92 
6.3.5 Prestalk Cell Heterogeneity and the Signals that Direct 
Morphogenetic Cell Movement in the Multicellular Stages 92 
6.4 Terminal Differentiation and Spore Germination 94 
6.4.1 The Control of Culmination by Ammonia 94 
6.4.2 Activation of PKA 94 
6.4.3 Regulation of Spore Germination 95 
6.5 Outlook 95 
6.6 Summary 96 
References 96 
7 The Cell Division Cycle in Aspergillus nidulans 
John Doonan 99 
7.1 Introduction 99 
7.2 Common Features of the Eukaryotic Cell Division Cycle 99 
7.3.1 The Cell Division Cycle in Aspergillus 100 
7.3.2 Mitosis in Aspergillus 101 
7.4 Studying the Cell Cycle in Aspergillus: Methodology 103 
7.4.1 Observing Mitosis 103 
7.4.2 Genetic Tools for Looking at the Cell Division Cycle 105 
7.4.3 DNA-Mediated Transformation as a Tool 
to Manipulate Gene Expression 106 
7.4.4 Protein Surveillance: Epitope Tagging 
and Green Fluorescent Protein 107 
7.5 Different Classes of Genes Required for Cell Division 107 
7.5.1 Never in Mitosis Mutants 107 
7.5.2 Blocked in Mitosis Mutants 109 
7.5.3 Septation-Defective Mutants 111 
7.5.4 Genome Integrity Mutants 111 
7.6 Regulatory Circuits Controlling the Nuclear Division Cycle 111 
7.6.1 Entry into Mitosis 112 
7.6.2 Coupling Mitosis and the Completion of S-Phase 112 
7.6.3 The Replication Complex and Preventing Mitosis 
Occurring in G1/S 113 
7.6.4 Completion of Mitosis and Septum Formation 113 
7.7 Outlook and Summary 114 
References 114 
Section 2 Plants 
8 Flowering Plant Embryogenesis 
Casper Vroemen and Sacco de Vries 121 
8.1 Introduction 121 
8.2 Pattern Formation, Cell Differentiation 
and Organ Development in the Plant Embryo 121 
8.2.1 The Apical-Basal Pattern 122 
8.2.2 The Orientation of the Apical-Basal Embryo Axis 
Is not Fixed Before Fertilization, and May Be Influenced 
by Surrounding Maternal Tissue 124 
8.2.3 The Establishment of the Apical-Basal Pattern Proceeds in Steps 
and May Require Signalling Between Early Embryonic Regions 124 
8.2.4 The Radial Pattern 125 
8.2.5 The Establishment of the Preliminary Radial Pattern 
Proceeds from Outside to Inside and Requires 
the Proper Separation of Tissue Layers 125 
8.2.6 The Elaboration of the Preliminary Radial Pattern Requires 
Fate-Specifying and Cell-Division Genes 126 
8.2.7 The Shoot Apical Meristem 126 
8.2.8 Genes Involved in the Establishment and Partitioning 
of the Shoot Apical Meristem 127 
8.2.9 The Root Meristem 128 
8.3 The Hormone Auxin Seems Involved in Pattern 
and Organ Formation 129 
8.4 The Initiation and Early Division Pattern 
of Plant Embryogenesis Are Flexible 129 
8.5 Genes Controlling the Initiation of Somatic Embryos 130 
8.6 Outlook 131 
8.7 Summary 131 
References 131 
9 Root Development in Arabidopsis 
Liam Dolan 133 
9.1 Introduction 133 
9.2 Two Meristems Are the Product of Embryogenesis 
in Arabidopsis 133 
9.3 The Cellular Organization of the Primary Arabidopsis Root 133 
9.4 Tissues of the Root Are Derived from a Set of Initial Cells 
in the Meristem 135 
9.5 Laser Microsurgical Experiments Indicate 
that Positional Information in the Cell Wall Is a Primary Factor 
in the Determination of Cell Fate 135 
9.6 Central Cells Negatively Regulate the Differentiation 
of Initial Cells 136 
9.7 Initial Cell Fate Is Specified by Positional Information 136 
9.8 Positional Information Directs Cell Fate in the Epidermis 137 
9.9 Positional Information Is Organized 
with Defined Spatial Boundaries 137 
9.10 SCARECROW and SHORT ROOT Are Required 
for the Development of Radial Pattern 137 
9.11 SCR and SHR Activity Are Required for the Division 
of the Cortical Daughter Cell in the Primary Root 138 
9.12 TRANSPARENT TESTA GLABRA and CAPRICE Specify Fate 
in the Epidermis 139 
9.13 Lateral Root Development Requires Auxin 139 
9.14 Auxin Is Required Throughout the Development 
of Lateral Roots 140 
9.15 Environmental Factors Modulate Lateral Root Development 141 
9.16 Nitrate Is a Signalling Molecule Involved in the Root Response 
to Local Elevated Levels of the Ion 141 
9.17 Outlook 141 
9.18 Summary 143 
References 143 
10 Leaf Development 
Carlo Pozzi, Kai J. Mller, Wolfgang Rohde, 
and Francesco Salamini 145 
10.1 Introduction 145 
10.2 Leaf Morphology 146 
10.3 Leaf Development and its Genetics 146 
10.3.1 Stages of Leaf Development 146 
10.3.2 Primordium Initiation 147 
10.3.2.1 Position 147 
10.3.2.2 Meristem Zonation and Leaf Primordium Initiation 148 
10.3.3 Maturation of Leaf Primordia 150 
10.3.3.1 The Maturation Schedule 150 
10.3.3.2 The Role of Cell Division 153 
10.3.4 Developmental Aspects and Symmetries 
of the Dicotyledonous Primordium and Leaf 153 
10.3.5 Leaf Expansion and Regional Cell Differentiation 154 
10.3.5.1 Leaf Expansion 154 
10.3.5.2 Epidermis 155 
10.4 Molecular Aspects of Leaf Development 157 
10.4.1 Homeobox Genes 157 
10.4.2 Homeobox Gene Redundancy 159 
10.4.3 Compound Leaves 160 
10.5 Summary and Outlook 163 
References 164 
11 Floral Development: Genetic Views and Molecular News 
Brendan Davies, Hans Sommer, 
and Zsuzsanna Schwarz-Sommer 167 
11.1 Introduction 167 
11.2 The First Steps Towards Flower Formation 167 
11.2.1 Angiosperm Shoot Development: 
Vegetative and Reproductive Meristems 167 
11.2.2 Genetic Control of Flower Initiation 168 
11.3 Genetic Control of Floral Organ Identity by Homeotic Genes 169 
11.3.1 The Simple ABC Model 169 
11.3.2 Testing the ABC Model in Arabidopsis and Antirrhinum 171 
11.3.3 Class A Genes and the FLIP 171 
11.3.4 Class B and Class C Genes in the Control of Cell Division 172 
11.3.5 Differences in Antirrhinum and Arabidopsis B and C Functions 172 
11.3.6 The Control of Morphological 
and Gene Expression Boundaries 173 
11.4 MADS-Box Factors at the Molecular Level 174 
11.4.1 Structure of Plant MADS-Box Factors 174 
11.4.2 Protein-Protein Interaction 175 
11.4.3 Regulation of MADS-Box Gene Expression 176 
11.4.4 Target Genes 176 
11.5 The Organ Identity Genes in Other Species: 
Facts and Speculations 177 
11.5.1 The Number of Genes Involved in Class B and C Functions 177 
11.5.2 Class B and C Genes and Sex Determination? 177 
11.5.3 Divergent Spatial and Temporal Flower Development 179 
11.6 Practical Applications of Plant MADS-Box Genes 180 
11.6.1 Altering Plant and Flower Structure, Colour and Timing 
of Flowering 180 
11.6.2 Genetic Engineering of Parthenocarpic Plants 
and Improvement of Fruit Set 180 
11.7 Outlook 181 
11.8 Summary 182 
References 182 
12 Genetic Control of Endosperm Development 
Stephen Slocombe, Monika Maitz, Gregorio Hueros, 
Heinz-Albert Becker, Guo Yan, Martin Mller, 
Serena Varotto, Geraldina Santandrea, 
and Richard D. Thompson 185 
12.1 Introduction 185 
12.2 Differentiation of the Endosperm 185 
12.2.1 Determination of Endosperm Cell Types 185 
12.2.2 Domains of Gene Expression 187 
12.2.3 Regulation of Aleurone Gene Expression 189 
12.3 Regulation of Solute Transfer into the Seed: 
Role of the Transfer Layer 190 
12.4 Regulation of Storage Product Accumulation: 
Role of the Central Endosperm 191 
12.4.1 Mutants Affecting Storage Protein Deposition 191 
12.4.2 Transcriptional Regulation of Storage Product Deposition 192 
12.4.3 Regulation by Phytohormones and Nutrient Supply 194 
12.4.4 Development of Dessication Tolerance 194 
12.5 Outlook 195 
12.6 Summary 195 
References 195 
13 Environmental Light Signals and the Development 
of Arabidopsis 
Giorgio Morelli and Ida Ruberti 199 
13.1 Introduction 199 
13.2 Plant Responses to Light 199 
13.3 Arabidopsis Photomorphogenesis 201 
13.3.1 Photoreceptors and Downstream Regulators 
of Photomorphogenesis 201 
13.3.2 Role of Photoreceptors and Downstream Components 
in the Control of Hypocotyl Elongation During Deetiolation 202 
13.3.3 Role of Photoreceptors and Downstream Components 
in the Shade-Avoidance Response 204 
13.4 Arabidopsis Flowering 206 
13.4.1 Photoperiodism 206 
13.4.2 Long-Day-Promotion Pathway 207 
13.5 Summary and Outlook 208 
References 209 
14 Plant-Microorganism Symbiosis 
J. Allan Downie and Nicholas J. Brewin 211 
14.1 Introduction 211 
14.2 Exchange of Signalling Molecules 214 
14.2.1 Regulation of Bacterial Nodulation Genes 214 
14.2.2 Biosynthesis of Nod Factors 215 
14.2.3 Determination of Host Specificity 215 
14.3 Nodule Organogenesis 219 
14.3.1 Initial Signalling Events in Root Cells 219 
14.3.2 Nodule Meristem Initiation 221 
14.3.3 Phytohormones 222 
14.4 Infection 223 
14.4.1 Infection Thread Development 223 
14.4.2 Bacterial Release 224 
14.5 Nodule Organogenesis 224 
14.5.1 Tissue and Cell Development 224 
14.5.2 Differentiation of the Symbiosome Compartment 226 
14.6 Summary and Outlook 228 
References 229 
Section 3 Animals 
15 Caenorhabditis elegans: Embryonic Axis Formation; 
Signalling in Early Development 
Craig P. Hunter 233 
15.1 Introduction 233 
15.2 Overview of Axis Formation and Early Embryogenesis 234 
15.2.1 Fertilization and the First Mitotic Division 234 
15.2.2 The Three Embryonic Axes 235 
15.2.3 Cell Signals and Asymmetrically Segregated Molecules 235 
15.2.4 The Gene Activities That Pattern the Early Embryo Specify 
Blastomere Identity 236 
15.3 Establishing Anterior-Posterior Polarity in the Zygote 236 
15.3.1 The Sperm Entry Position Determines the Posterior Pole 236 
15.3.2 Cytoplasmic Reorganization Is Dependent on Microfilaments 237 
15.3.3 Gene Activities Required for Embryonic Polarity 238 
15.3.3.1 Spindle Orientation in the 2-Cell Embryo 238 
15.3.3.2 The PAR Proteins Are Asymmetrically Localized 239 
15.4 Specifying Posterior Blastomere Fates 240 
15.4.1 SKN-1 and PAL-1 Are Posteriorly Localized Blastomere 
Specification Proteins 240 
15.4.2 skn-1 Regulates pal-1 Activity in EMS But Not in P_2 240 
15.4.3 PIE-1 Protein Localizes to the Germ Lineage 
and Its Activity Inhibits Transcription 240 
15.4.4 Linking Asymmetric Cleavage to Differential Gene Activity 242 
15.5 Cell Interactions That Specify Blastomere Identity: 
Polarizing Cell Signals Revealed 242 
15.5.1 The Polarity of the Dorsal-Ventral Axis Is Specified 
by Cell Signals 242 
15.5.2 Signal No. 1: A Signal from P2 Specifies the AB.p Lineage 242 
15.5.3 Signal No. 2: Left-Right Polarity Can Be Reversed 
by Exchanging Cell Positions 243 
15.5.4 GLP-1 Is a Receptor for Both the P_2 Signal and the MS Signal 243 
15.5.5 APX-1 Is the P_2 Ligand 243 
15.5.6 Signal No. 3: The P_2 Blastomere Also Polarizes 
the EMS Blastomere 244 
15.5.7 Mutations Defective in P_2 EMS Interactions Identify 
Conserved wnt Pathway Genes 245 
15.6 Controlling the Expression Patterns of Blastomere 
Specification Proteins 246 
15.6.1 Spatial and Temporal Control of PAL-1 Translation 246 
15.6.2 Localizing Other Blastomere Specification Proteins 247 
15.6.3 Maternal Control of Embryonic Patterning 
Is Non-Hierarchical in C. elegans 248 
15.7 Outlook 249 
15.8 Summary 249 
References 249 
16 Cell Fate Determination in Caenorhabditis elegans 
Michael Krause 251 
16.1 Introduction 251 
16.2 Overview of C. elegans Development 251 
16.3 Founder Blastomere Rate Specification 253 
16.4 Zygotic and Larval Somatic Cell Fate Determination 255 
16.4.1 Determinants and Terminal Cell Fate Specification 255 
16.4.2 Clues to Fate Determination from the Lineage 256 
16.4.3 Asymmetry and Diversification Within a Lineage 257 
16.4.4 Equivalence Groups 260 
16.5 Molecular Genetics of Cell Fate Determination 260 
16.5.1 Specification of Intestinal Cells 261 
16.5.2 The Male Tail as a Model for Cell Fate Specification 
and Morphogenesis 263 
16.6 Outlook 266 
16.7 Summary 266 
References 267 
17 Morphogenesis and Organogenesis in Caenorhabditis elegans 
Lois G. Edgar 269 
17.1 Introduction 269 
17.2 Embryonic Morphogenesis in C. elegans 270 
17.2.1 Summary of Embryonic Development from the Viewpoint 
of Morphogenesis 270 
17.2.2 Early Shaping: Gastrulation and the Refinement of Body Axes 273 
17.2.2.1 What Initiates Gastrulation? 274 
17.2.2.2 Late Gastrulation: Ventral Cleft Closure 274 
17.2.3 Hox Gene Functions in Morphogenesis 275 
17.2.4 Hypodermal Morphogenesis 277 
17.2.4.1 Hypodermal Origins and Early Patterning 277 
17.2.4.2 Ventral Hypodermal Closure 278 
17.2.4.3 Elongation 278 
17.2.5 Genetic Control of Hypodermal Morphogenesis 
and Elongation 281 
17.2.5.1 Genes Functioning in the Pattern Formation Phase 281 
17.2.5.2 Genes Functioning in Hypodermal Cell Movements 283 
17.2.5.3 Genes Involved in Elongation 283 
A Signalling/Regulatory Pathway 283 
Structural Genes Required for Elongation 284 
17.2.6 Muscle Morphogenesis and Hypodermal Interactions 285 
17.2.6.1 Body Wall Muscle Formation 285 
17.2.6.2 Extracellular Membranes: the Connection Between Muscle 
and Hypodermis 286 
17.2.6.3 Genetic Analysis of Muscle Morphogenesis 288 
17.2.7 Morphogenesis of the Digestive System 288 
17.2.7.1 Morphology 288 
17.2.7.2 Origins of the Digestive System 289 
17.2.7.3 Organ Identity: the Pharynx 290 
17.2.7.4 Gut Morphogenesis 291 
17.3 Postembryonic Morphogenesis 291 
17.3.1 Morphogenesis of the Male Tail 292 
17.4 Outlook 292 
17.5 Summary 293 
References 294 
18 The Regulation of Cell and Growth Cone Migrations 
During the Development of Caenorhabditis elegans 
William G. Wadsworth 299 
18.1 Introduction 299 
18.1.1 Caenorhabditis elegans as a Model 
for Nervous System Development 299 
18.2 Neurogenesis 300 
18.2.1 Neuroglia and Basement Membrane Formation 300 
18.2.2 Development of the Axon Scaffold 302 
18.3 Guidance Cues Provide Directional Information 302 
18.3.1 The Model of Hierarchical Guidance Cues 303 
18.3.2 Axon Scaffold Development Requires Multiple Guidance Cues 303 
18.4 Receptors, Signaling Pathways, and Cytoskeletal Adaptors 
Direct Cellular Responses 304 
18.4.1 Receptors Mediate Pathway Selection 304 
18.4.2 Cell-Substrate Interactions Regulate Adhesive Properties 305 
18.4.3 The Cytoskeleton Is Coupled to Signal Transduction Pathways 306 
18.5 Extracellular Signals Coordinate Nervous Tissue Formation 
and Migrations 307 
18.6 Outlook 308 
18.7 Summary 308 
References 309 
19 Formation of Embryonic Axes and Blastoderm Pattern 
in Drosophila 
Martin Klingler and Diethard Tautz 311 
19.1 Introduction 311 
19.2 The Blastoderm Fate Map 313 
19.3 Four Maternal Gradients Provide Spatial Information 
for the Embryo 314 
19.4 Linear Pathways Generate the Maternal Gradients 316 
19.5 Symmetry Breaking and Oocyte Polarity 320 
19.6 A Network of Zygotic Genes Creates the Blastoderm Fate Map 321 
19.6.1 Gap Genes 321 
19.6.2 Pair-Rule Genes 322 
19.6.3 Segment Polarity Genes 324 
19.7 The Interpretation of Positional Information 324 
19.8 Patterning Accuracy and Size Regulation 327 
19.9 Outlook 327 
19.10 Summary 328 
References 329 
20 Early Neurogenesis in Drosophila 
Jos A. Campos-Ortega 331 
20.1 Introduction 331 
20.2 Cellular Aspects of Neurogenesis 332 
20.2.1 The Formation of the Neuroectoderm 
and the Segregation of Neuroblasts 332 
20.2.2 The Pattern of Neuroblasts 332 
20.2.3 The Proliferation of the Neuroblasts 334 
20.2.4 The Neuroblast Lineages 335 
20.3 Genetic Aspects of Neurogenesis 335 
20.3.1 The Genetic Network That Regulates Early Neurogenesis 335 
20.3.2 The Neural Decision Is Controlled by the Proneural Genes 336 
20.3.3 Physical Interactions of Notch and Delta 337 
20.3.4 The Transduction of the Regulatory Signals 339 
20.3.5 The Target of Notch Activation Is the E(SPL)-C 340 
20.3.6 Proneural Genes Activate Neurogenic Genes 340 
20.4 Evolutionary Conservation of the Regulatory Network 341 
20.5 Outlook 342 
20.6 Summary 342 
References 342 
21 Drosophila: Imaginal Disk Development: 
Patterning the Adult Fly 
Seth S. Blair 347 
21.1 Introduction 347 
21.2 Techniques 349 
21.2.1 Cell and Tissue Markers 349 
21.2.2 Mutations and Mosaic Analysis 349 
21.2.3 Misexpressing Genes 351 
21.3 Cell Lineage and Compartments in Wild-Type Discs 351 
21.4 Compartment Identity and "Selector" Genes 352 
21.4.1 engrailed, invected, and the A/P Boundary 352 
21.4.2 apterous and the D/V Boundary 353 
21.5 HEDGEHOG Signalling Across the A/P Boundary 353 
21.6 DECAPENTAPLEGIC and Anterior-Posterior Patterning 
Within Compartments of the Wing 355 
21.7 Fine-Scale Anterior-Posterior Wing Patterning: 
Vein Formation 357 
21.8 WINGLESS; DECAPENTAPLEGIC, and Patterning 
in the Leg and Antenna 359 
21.8.1 Dorso-Ventral Sectors and Circumferential Patterning 359 
21.8.2 Proximo-Distal Patterning 359 
21.9 NOTCH Signalling Across the D/V Boundary of the Wing 361 
21.10 Wing Margin WINGLESS and Patterning Within the Dorsal 
and Ventral Compartments 362 
21.11 Mechanisms Underlying Compartmental Lineage Restrictions 363 
21.12 Tissue Polarity 363 
21.13 Development of the Imaginal Disc Primordia 364 
21.14 Disc Specific Identities 365 
21.14.1 Homeotic Mutations 365 
21.14.2 Transdetermination 365 
21.15 Disc Growth Control and Overgrowth Mutations 366 
21.16 Regeneration of Discs 366 
21.17 Outlook 367 
21.18 Summary 367 
References 367 
22 Insertional Mutagenesis in Zebrafish 
Adam Amsterdam and Nancy Hopkins 371 
22.1 Introduction 371 
22.2 Large-Scale Chemical Mutagenesis in Zebrafish 372 
22.2.1 Large-Scale Screens 372 
22.2.2 Prospects for Cloning Chemically Mutated Genes 374 
22.3 Insertional Mutagenesis in Other Animals 375 
22.4 Transgenesis in Zebrafish 376 
22.4.1 Microinjection of Plasmid DNA 376 
22.4.2 Infection with Pseudotyped Retroviral Vectors 376 
22.5 Efficiency of Retroviral Vectors as Mutagens: a Pilot Screen 378 
22.6 Cloning the Insertionally Mutated Genes 379 
22.7 Positions of Mutagenic Insertions 381 
22.8 Outlook 382 
22.8.1 General Applicability of Retroviral Insertional Mutagenesis 
in Zebrafish 382 
22.8.2 Conducting a Large-Scale Insertional Mutagenesis Screen 
in the Fish 382 
22.8.3 Areas for Improvement in the Technology 385 
22.9 Summary 386 
References 387 
23 Spatial and Temporal Control of Maternal Message Utilization 
Davor Solter and Barbara B. Knowles 389 
23.1 Introduction 389 
23.2 Maternal Messages in Non-Mammalian Species 389 
23.3 Maternal Messages in Mammals 390 
23.4 Coda 392 
23.5 Summary and Outlook 392 
References 392 
24 DNA Methylation 
Peter W. Laird 395 
24.1 Introduction to Epigenetics and DNA Methylation 395 
24.1.1 Epigenetics and Development 395 
24.1.2 Epigenetic Mechanisms 395 
24.1.3 Eukaryotic DNA Methylation 396 
24.1.4 Eukaryotic DNA Methyltransferase Genes 397 
24.1.5 Demethylation 399 
24.2 Patterns of DNA Methylation 399 
24.2.1 CpG Islands 399 
24.2.2 Developmental Patterns 399 
24.2.3 Tissue Culture Patterns 400 
24.2.4 Aging Patterns 401 
24.2.5 Cancer Patterns 401 
24.2.6 Experimental Detection of Patterns 401 
24.2.7 Experimental Manipulation of Patterns 402 
24.3 Functional Consequences of DNA Methylation 402 
24.3.1 Gene Expression 402 
24.3.2 X-Inactivation 403 
24.3.3 Genomic Imprinting 403 
24.3.4 Host Defense 404 
24.3.5 Mutagenesis 404 
24.4 Summary and Outlook 405 
References 405 
25 X-Chromosome Inactivation 
Jeannie T. Lee 407 
25.1 Introduction 407 
25.2 X-Inactivation During Mammalian Development 409 
25.3 X-Inactivation Involves Changes in Chromatin Structure 410 
25.4 Toward a Molecular Understanding of X-Inactivation 412 
25.5 Exceptions to the Rule: Escape from X-Inactivation 415 
25.6 X-Inactivation in the Male Germ Line 415 
25.7 Outlook and Summary 417 
References 417 
26 Genomic Imprinting: Its Role in Development and Disease 
Johanna A. Joyce and Anne C. Ferguson-Smith 421 
26.1 Introduction 421 
26.2 Developmental Consequences of Imprinting 421 
26.3 Only Some Chromosomes Are Imprinted 422 
26.4 Imprinting Defects Can Cause Human Disease 423 
26.4.1 Uniparental Disomy 424 
26.4.2 Prader-Willi and Angelman Syndromes 424 
26.4.3 Beckwith-Wiedemann Syndrome 426 
26.5 Several Approaches Have Resulted in the Identification 
of Imprinted Genes 426 
26.5.1 Targeted Mutagenesis of Known Genes 426 
26.5.2 Systematic Screens for Imprinted Genes 427 
26.5.2.1 Restriction Landmark Genomic Scanning (RLGS) 427 
26.5.2.2 cDNA Subtraction Hybridization 427 
26.5.2.3 Allelic Message Display 427 
26.6 The Molecular Mechanisms of Imprinting 427 
26.6.1 DNA Methylation Is Important for Imprinting 428 
26.6.2 Regional Controlling Elements and Expression Competition 
Regulate Imprinting 430 
26.6.3 Chromatin Effects in Imprinted Domains 430 
26.6.3.1 Evidence for Parental Differences in Chromatin Structure 430 
26.6.3.2 Histone Acetylation on Parental Chromatin 430 
26.6.3.3 Many Imprinted Genes Contain Repetitive Sequences 431 
26.7 Outlook 431 
26.8 Summary 432 
References 433 
27 Myogenesis 
Michael A. Rudnicki 435 
27.1 Introduction 435 
27.1.1 The Embryonic Origin of Skeletal Muscle 435 
27.1.2 The Embryonic Induction of Myogenesis 436 
27.1.3 Myogenesis in Limb Buds 436 
27.1.4 Different Embryonic Lineages Contribute to Muscle 436 
27.2 The MyoD Family of Regulatory Factors 437 
27.2.1 MyoD-Family Expression Suggests a Functional Classification 437 
27.2.2 Relatedness of the Primary and Secondary Myogenic 
Regulatory Factors 437 
27.3 The MyoD Family Are bHLH Transcription Factors 438 
27.3.1 Dimerization Is Required for MyoD-Family Function 438 
27.3.2 Mitogens Regulate MyoD-Family Activity 439 
27.3.3 The MEF2 Family of Transcription Factors 439 
27.3.4 The Rb Family and Myogenesis 439 
27.4 The Function of the MyoD Family During Embryogenesis 440 
27.4.1 Myf-5 and MyoD Are Determination Factors 440 
27.4.2 Myogenin and MRF4 Are Differentiation Factors 441 
27.4.3 Analysis of MyoD-Family Mutations Supports 
the Lineage Hypothesis 441 
27.5 Regeneration of Skeletal Muscle 442 
27.6 Outlook 443 
27.7 Summary 444 
References 444 
28 Neurotrophins in Development of the Nervous System 
Ernest Arenas and Patrik Ernfors 447 
28.1 Introduction 447 
28.2 Neurotrophins 447 
28.3 Neurotrophin Receptors 448 
28.3.1 Tyrosine Kinase Neurotrophin Receptors 448 
28.3.2 The Low Affinity Neurotrophin Receptor 450 
28.3.3 Receptor Isoforms and Functions 450 
28.4 Requirement of Different Functional Classes 
of Sensory Neurons on Specific Neurotrophins 451 
28.5 A Target-Derived Source of Neurotrophins in the Peripheral 
Nervous System and the Control of Axonal Branching 454 
28.6 Neurotrophins and Neurogenesis 
in the Peripheral Nervous System 455 
28.7 Neurotrophin Switching in the Peripheral Nervous System 455 
28.8 Neurogenesis, Migration and Specification of Neurotransmitter 
Phenotype in the Central Nervous System 455 
28.9 Neuronal Survival and Development of Axonal and Dendritic 
Functional Domains in the Central Nervous System 457 
28.10 Synaptic Plasticity in the Central Nervous System 458 
28.11 From Studies on Nervous System Development to Therapeutic 
Agents in Neurodegenerative Diseases 458 
28.11.1 The Inner Ear 459 
28.11.2 The Locus Coeruleus 
28.12 Summary and Outlook 460 
References 460 
29 Olfactory Receptor Gene Regulation 
Andrew Chess 463 
29.1 Introduction 463 
29.1.1 Odorant Receptor Genes 463 
29.1.2 Receptor Expression in Individual Neurons 463 
29.1.3 A Topographic Map 464 
29.2 Transcriptional Regulation 464 
29.2.1 One Olfactory Receptor Gene (OR) Is Expressed Per Neuron 464 
29.2.2 Chromosomal Arrays of OR Genes 465 
29.2.3 Monoallelic Expression 465 
29.2.4 Asynchronous Replication 465 
29.3 A Model for Odorant Receptor Gene Regulation 466 
29.4 Evolution and the Regulation of the Genes 468 
29.5 Choice of Receptor and Axon Guidance 468 
29.6 Outlook 469 
29.7 Summary 469 
References 470 
30 Genetically Modified Mice as Tools for Cancer Research 
Erwin F. Wagner and Zhao-Qi Wang 471 
30.1 Introduction 471 
30.2 Genetically Modified Mice to Study Tumor Development 472 
30.3 Transgenic Mouse Models of Human Tumors 474 
30.3.1 Skin Cancer 474 
30.3.2 Pancreatic Cancer 476 
30.3.3 Bone Tumors 476 
30.4 Role of Tumor Suppressor Genes (TSGs) 478 
30.4.1 Mice Deficient in p53 and Retinoblastoma Protein (Rb) 478 
30.4.2 Mice Lacking Breast Cancer Susceptibility Genes BRCA1 
and BRCA2 478 
30.4.3 Mice with APC Gene Mutations 480 
30.4.4 Mice Carrying Disrupted DNA Repair Genes 480 
30.5 Mouse Models to Study Environmental Carcinogenesis 481 
30.5.1 Skin Carcinogenesis 481 
30.5.2 Liver Cancer 481 
30.5.3 The p53 Knock-Out Mouse Model 481 
30.5.4 Indicator Mice 482 
30.6 Summary and Outlook 482 
References 483 
31 Circadian Timing in Animals 
Ueli Schibler and Daniel J. Lavery 487 
31.1 Introduction 487 
31.1.1 Anticipation of the Next Day 487 
31.1.2 Input - Oscillator - Output 487 
31.1.3 Experimental Evidence for Endogenous Clocks 488 
31.1.4 Light-Induced Phase Shifting and Phase Response Curves 489 
31.2 Master Clocks and Peripheral Clocks 490 
31.2.1 Circadian Master Clocks Are Associated with Certain Tissues 490 
31.2.2 The Pineal Gland Has Distinct Functions 
in Different Vertebrates 491 
31.2.3 The Suprachiasmatic Nucleus: A Mammalian Master Clock 491 
31.2.4 Circadian Oscillations Are Produced 
by Cell-Autonomous Mechanisms 492 
31.3 The Parameters of the Clock Are Genetically Defined 492 
31.3.1 Evidence for Clock Genes in Animals 292 
31.3.2 The Drosophila Clock Genes per, tim, clk, cyc, and dbt 493 
31.3.3 Genes and Loci Involved in Mammalian Circadian Timing 496 
31.4 Circadian Physiology in Mammals 496 
31.4.1 Outputs: Vital Body Functions Are Under Clock Control 496 
31.4.2 Genes Controlling Circadian Outputs in the Periphery 497 
31.4.3 Entrainment of Peripheral Clocks 499 
31.5 Outlook 499 
31.6 Summary 502 
References 503 
32 Polarity in Biological Systems 
David J. Cove, Ian A. Hope, and Ralph S. Quatrano 507 
32.1 Introduction 507 
32.2 Biological Polarity and Scale 507 
32.2.1 Polarity at the Level of the Whole Organism 507 
32.2.2 Polarity at the Level of the Organ 509 
32.2.3 Polarity at the Level of the Single Cell 511 
32.2.4 Polarity at the Subcellular Level 511 
32.2.5 Polarity at the Level of the Single Molecule 511 
32.3 The Generation of Polarity 512 
32.3.1 Self-Assembly Can Generate a Polar Structure 512 
32.3.2 The Orientation of a Polar Axis May Be Determined 
by Chance 512 
32.3.3 The Establishment of Chirality May Pose Special Problems 514 
32.3.4 External Inputs Often Generate Polarity 515 
32.4 The Perpetuation of Polarity 518 
32.5 The Modification of Polarity 519 
32.6 Outlook 523 
32.7 Summary 523 
References 523 
Glossary 525 
Subject Index 537 
END
