Hox Genes (eBook)

JEAN S. DEUT SCH, is Emeritus Professor of Genetics and Animal Biology, Université Pierre et Marie Curie, Paris 6, Department (UMR 7622) “Biologie du Développement”. Under the supervision of Prof. P.P. Slonimski, he participated to the birth of mitochondrial genetics of the yeast Saccharomyces cerevisiae. During the ‘80s, he moved to the Institut Jacques Monod in Paris to study developmental genetics of Drosophila melanogaster, focusing on the genetics of the hormonal control of metamorphosis. In 1993, he was the first in France, together with André Adoutte, to undertake evo-devo studies, choosing the cirripedes, which have been Darwin’s favourite animals, as a model, because of their so peculiar body plan. In a second step, his team studied the developmental genetics of other arthropods, including scorpions and pycnogonids. He is author of a number of scientific publications in international journals, and of three textbooks in French on Drosophila and genetics.

Title Page 3
Copyright Page 4
FOREWORD 5
PREFACE 8
ABOUT THE EDITOR... 11
PARTICIPANTS 12
Table of Contents 15
ACKNOWLEDGEMENTS 19
SECTION I Mechanisms of Activity 20
Chapter 1 Regulation of Hox Activity: Insights from Protein Motifs 21
Introduction 21
The Homeodomain 22
Phylogeny of Hox Genes and General Features of Hox Homeodomains 22
Specificity of Hox Homeodomain DNA Binding 23
Activity Regulation of Hox Homeodomains 25
Homeodomain-Mediated Transport 25
The Hexapeptide Motif 26
Cofactor Mediated Control of Hox Target Gene Specificity 26
PBC-Independent Functions for the Hexapeptide Motif 27
Additional Hox Functional Motifs 27
Alternate Motifs for PBC Recruitment? 27
The Linker Region: A Variable but Crucial Hox Protein Domain 27
Transcriptional Activation and Repression Domains 28
Conclusion 28
References 30
Chapter 2 Cis-Regulation in the Drosophila Bithorax Complex 35
Genetics of the Bithorax Complex: The Model of Ed Lewis 35
The BX-C Encodes Only Three Genes, Ubx, abd-A and Abd-B 37
The Segment-Specific Functions Act as Segment/ Parasegment-Specific Enhancers 40
Initiation and Maintenance Phase in BX-C Regulation 41
Initiation, Maintenance and Cell Type-Specific Elements within the Cis-Regulatory Domain 43
The Cis-Regulatory Regions Are Organized in Segment-Specific Chromosomal Domains 44
Chromatin Boundaries Flank the Parasegment-Specific Domains 46
Elements Mediating Long-Distance Cis- and Trans- Regulatory Interactions 46
Transvection Studies 46
Promoter Targeting Sequences 49
Promoter Tethering Element 50
Intergenic Transcription in the BX-C 50
MicroRNAs in the BX-C 52
Conclusion 53
References 54
Chapter 3 Maintenance of Hox Gene Expression Patterns 59
Introduction 59
Genetics of PcG and trxG Genes 60
PcG Proteins and Their Complexes 61
TrxG Proteins and Their Complexes 64
ETP Proteins 64
PcG and trxG Response Elements 65
Recruitment of Maintenance Proteins to Maintenance Elements 66
Role of Maintenance Proteins in Regulation of Transcription 68
Epigenetic Marks 69
Release of PcG Silencing 71
Role of PcG Proteins in Chromatin Replication 72
Role of PcG Proteins in Stem Cells 72
Conclusion 73
Future Research in the Field 73
References 74
Chapter 4 Control of Vertebrate Hox Clusters by Remote and Global Cis-Acting Regulatory Sequences 81
Introduction 81
Colinearity and Clustering of the Homeotic Genes: An Obligatory Functional Link? 82
Vertebrate Hox Clusters Are More Clustered Than Others 83
Global Regulation of the Complex through Shared Mechanisms: The Retinoic Acid Connection 84
High-Order Structures Over the Complex and Colinearity 84
Control of Vertebrate Hox Genes by Shared Internal Enhancers 85
The Ins and Outs of Hoxd Gene Regulation 85
The Role of the Flanking Regions in the Control of Vertebrate Hox Genes 86
Control of the HoxD Cluster through Remote Enhancers 87
Regulation of the HoxD Cluster and More: Global Control Regions and Regulatory Landscapes 88
Remote Enhancers for the Other Vertebrate Hox Clusters? 89
An Evolutionary Success Story and an Increasing Need for a Global Regulation 91
Conclusion and Outlook for Hox Gene Regulation in the 21st Century 92
References 93
SECTION II Evolution of Hox Genes and Complexes 97
Chapter 5 The Early Evolution of Hox Genes: A Battle of Belief? 98
The Hox System 98
Phylogenetic Evidence 99
Opposing Views 101
Differences in Assigning Gene Homology 101
Linkage Data 103
Expression Data 104
Conclusion 104
References 106
Chapter 6 Evolution of Hox Complexes 108
Introduction 108
Origin of the ProtoHox Gene 108
Origin of the Hox Cluster from a ProtoHox Cluster, or Not? 109
Number of Genes in a ProtoHox Cluster 109
Alternatives to a ProtoHox Cluster 110
Expansion and Contraction of the Number of Hox Genes in Evolution 113
Conclusion 115
References 115
Chapter 7 The Nematode Story: Hox Gene Loss and Rapid Evolution 118
Introduction: Hox Gene Loss, the Third Way 118
The Caenorhabditis elegans Hox Cluster, an Extreme Case of Gene Loss 119
Tracing Hox Gene Loss through the Nematode Phylum: Mode and Tempo 121
Sea Squirts and Nematodes: Why Do Both Groups Lose Hox Genes 122
Hox Gene Loss in Flagrante 123
Nematode Hox Gene Function: A Story of Novelty, Conservation and Redeployment 123
Conclusion 125
References 126
Chapter 8 Are the Deuterostome Posterior Hox Genes a Fast-Evolving Class? 128
The Distribution of the Posterior Hox Genes in the Metazoa 128
Problematic Assignments of Hox Genes as ‘Posterior’ 130
Early Duplications of the Posterior Hox Genes 130
The ‘Deuterostome Posterior Flexibility’ Hypothesis 131
Recent Analyses Broadly Support the Posterior Flexibility Hypothesis 132
The Mechanistic Basis of Deuterostome Posterior Flexibility 133
Faster Rates May Be Linked to Gene Duplications 133
Faster Rates May Be Linked to Morphological Evolution 134
Processes Other Than Faster Rates Might Be Operating 134
Conclusion and Future Directions 135
References 136
SECTION III Biological Function 140
Chapter 9 Hox Genes and the Body Plans of Chelicerates and Pycnogonids 141
Arthropods, Mandibulates vs Chelicerates 141
Chelicerate Hox Genes 142
Chelicerate Hox Genes and the Chelicerate vs Mandibulate Body Plan 143
Hox Genes and the Enigmatic Sea Spider Body Plan 146
Conclusion 147
References 147
Chapter 10 Hox3/zen and the Evolution of Extraembryonic Epithelia in Insects 149
Introduction 149
Setting the Stage: Morphological Evolution of Extraembryonic Development 150
Variants of zen Expression and Function in Insects and Possible Morphological Correlates 151
Suppression of Postgastrular zen Expression May Have Triggered the Origin of the Amnioserosa 153
Reduction of the Amniotic Anlage along the A-P Axis 154
Reduction of the Amniotic Anlage along the D-V Axis 154
Expression of zen in the Optic Field 156
The Amnioserosa Gene-Network in Evolutionary Perspective 156
Conclusion 157
References 158
Chapter 11 Hox Genes and Brain Development in Drosophila 161
Introduction 161
Expression and Function of Hox Genes in Embryonic Brain Development 162
Genetic Interactions between Hox Genes in Embryonic Brain Development 164
Hox Genes in Postembryonic Brain Development 165
Evolutionary Conservation of Hox Gene Action in Brain Development 167
Conclusion 168
References 168
Chapter 12 Homeosis and Beyond. What Is the Function of the Hox Genes? 170
What Are the Hox Genes? 170
The Hox Genes’ Explosion 171
What Is the Function of a Gene? 171
Hox Genes’ Function at the Molecular and Cellular Levels 172
Hox Genes and Homeosis 172
Homeosis as a Differential Function 172
Hox Genes as ‘Meta-Selector’ Genes 173
The Hox Specificity Paradox 173
Posterior Prevalence 174
An Evolutionary Paradox: Morphological Differentiation and the Hox Repertoire 174
Hox and Neuronal Homeosis 174
Morphological Homeosis as a Derived Property 175
Why Does the ‘Hox System’ Make Sense? 175
Conclusion 176
References 176
Index 181