| Preface | xii |
1. | Wnt Signal Transduction Pathways: An Overview | 1 |
| Abstract | 1 |
| Introduction | 1 |
| Wnt/[beta]-Catenin Signaling | 4 |
| The Wnt/Ca[superscript 2+] Pathway in Vertebrates | 8 |
| Planar Cell Polarity Signaling, or the Wnt/JNK Pathway | 8 |
| Outlook | 9 |
2. | Secreted Antagonists/Modulators of Wnt Signaling | 15 |
| Abstract | 15 |
| Introduction | 15 |
| Secreted Frizzled-Related Protein (sFRPs) | 16 |
| Domain Structure of sFRP | 16 |
| Mechanism of Wnt Signaling Modulation | 19 |
| Expression and Function of sFRP | 20 |
| Wnt-Inhibitory Factor-1 (WIF-1) | 20 |
| Cerberus | 21 |
| Dickkopf | 23 |
| Wingful/Notum in Drosophila | 28 |
| Conclusion | 30 |
3. | Wnt/Wingless Signaling in Drosophila | 35 |
| Abstract | 35 |
| Introduction | 35 |
| The Wg Pathway | 36 |
| Specificity in Wg Signaling | 40 |
| Does Wg Always Act as a Morphogen? | 42 |
| D WNT-4 Controls Cell Movement through a Unique Signaling Pathway | 42 |
4. | Wnt Signaling and the Establishment of the Dorsal-Ventral Axis in Xenopus | 47 |
| Abstract | 47 |
| Introduction | 47 |
| Cortical Rotation and Establishment of Asymmetry Along the Dorsal-Ventral Axis | 48 |
| Roles of Wnt and Frizzled in the Specification of Dorsal Cell Fates | 51 |
| Transport and Asymmetric Accumulation of Dishevelled | 54 |
| Stabilization of [beta]-Catenin on the Dorsal Side of the Embryo | 56 |
| [beta]-Catenin, XTCF-3, and Activation of Dorsal-Specific Gene Expression | 58 |
| The Destruction Complex and Ventral Inhibition of Wnt Signaling | 59 |
| Ventral Repression of Dorsal-Specific Genes | 62 |
| Ventral Inhibition of WNT/[beta]-Catenin Signaling by the Wnt/Ca[superscript 2+] Pathway | 62 |
| Other Potential Regulators of WNT Signaling during Axis Formation | 63 |
| A Working Model for the Function of Wnt Signaling in the Patterning of the Dorsal-Ventral Axis in Xenopus | 63 |
| Major Unresolved Issues | 65 |
5. | The Role of WNT Signaling in Vertebrate Head Induction and the Organizer-Gradient Model Dualism | 71 |
| Abstract | 71 |
| Introduction | 71 |
| The Vertebrate Organizer | 72 |
| Classical Models for Anteroposterior Axis Formation | 72 |
| Wnt/[beta]-Catenin Signaling Antagonizes the Vertebrate Head Organizer | 74 |
| Tissues with Posteriorizing Activity Express WNTs | 75 |
| The Two Inhibitor Model for Head Induction | 75 |
| Anterior Organizing Centers Express WNT Inhibitors | 79 |
| A Transforming Gradient of Wnt/[beta]-Catenin Activity Regulates AP Neural Patterning | 80 |
| Wnt Signaling and Gastrulation Movements | 81 |
| Later Roles of WNTs | 81 |
| Conclusions and Outlook | 82 |
6. | Epithelial Planar Cell Polarity in Drosophila | 90 |
| Abstract | 90 |
| Epithelial Planar Cell Polarity | 90 |
| Planar Cell Polarity in Drosophila | 91 |
| Wnt/Frizzled Signaling and Planar Cell Polarity Establishment | 92 |
| Frizzled Signaling and Its Link to the Other PCP Genes | 95 |
| Tissue Specific Responses to PCP Signaling | 97 |
| General and Evolutionary Implications | 99 |
7. | Patterning the Vertebrate Neural Plate by Wnt Signaling | 102 |
| Summary | 102 |
| Introduction | 102 |
| Induction of the Neural Plate | 104 |
| Anteroposterior Patterning of the Neural Plate | 106 |
| Dorsoventral Patterning of the Neuroepithelium | 107 |
| Neural Crest Induction and Diversification | 109 |
| Neural Crest Apoptosis | 111 |
| Conclusions | 112 |
8. | Wnts in Kidney and Genital Development | 117 |
| Abstract | 117 |
| Introduction | 117 |
| Kidney Development in the Mouse | 118 |
| Role of Wnt Genes in Metanephric Kidney Development | 122 |
| Wnt Signaling during Kidney Development--Perspectives from Studies in Alternative Vertebrate Models | 126 |
| Pro- and Mesonephric Kidneys as Simplified Models of Nephrogenesis | 127 |
| Wnt Signaling in the Pro- and Mesonephric Kidneys | 129 |
| Wnts in Kidney Organogenesis: Conclusions from a Multi-Species Approach | 131 |
| Genital Development in the Mouse | 133 |
| Role of Wnt Genes in Genital Development | 136 |
| Sexy Wnts: Losing Them Makes a Difference | 139 |
| A Wnty but Promising Future | 140 |
9. | Wnts in Muscle Development | 146 |
| Abstract | 146 |
| Introduction | 146 |
| Epithelialization of Paraxial Mesoderm and Somite Formation | 147 |
| Formation, Maintenance, and Patterning of the Dermomyotome | 147 |
| Epaxial Myogenesis | 149 |
| Hypaxial Myogenesis | 151 |
| Concluding Remarks | 152 |
10. | Wnt Signaling in Limb Development | 156 |
| Introduction | 156 |
| A Role for Wnt Signaling in Limb Bud Initiation | 157 |
| Wnt Signaling and Limb Bud Outgrowth | 159 |
| Limb Bud Patterning--A Role for Wnt Signaling in Establishing the Dorso-Ventral Axis and Beyond | 160 |
| Roles of Wnt Signaling in Appendicular Skeletogenesis | 162 |
11. | Wnt/Wg and Heart Development | 170 |
| Abstract | 170 |
| Introduction to Drosophila Cardiogenesis | 170 |
| Wg Signaling in Drosophila Cardiogenesis | 172 |
| Introduction to Vertebrate Cardiogenesis | 173 |
| Wnt Signaling in Vertebrate Cardiogenesis | 175 |
| Vertebrate Cardiogenesis Involves Different Wnt Signal Transduction Cascades | 176 |
| Conclusion and Future Perspectives | 179 |
12. | Wnt Signaling in C. elegans | 184 |
| Abstract | 184 |
| Introduction | 184 |
| Catalog of C. elegans Wnt Pathway Components | 184 |
| The Three C. elegans [beta]-Catenins Are Involved in Distinct Processes | 187 |
| A Canonical Wnt Pathway Controls the Migration of the Descendants of the QL Neuroblast | 188 |
| Embryonic Endoderm Introduction | 190 |
| Unusual Aspects of Wnt Signaling during Endoderm Induction | 191 |
| Wnt Signaling Might Directly Target the Cytoskeleton to Control Mitotic Spindle Orientation | 192 |
| Wnt and Ras Pathways Control P12 Cell Fate | 193 |
| Wnt Signaling in Vulval Development | 194 |
| An Unusual Wnt Pathway Controls T Cell Polarity | 197 |
| Gonad Polarity | 200 |
| Wnt Pathways Might Interact to Control V5 Cell Polarity | 202 |
| Sensory Ray Formation | 203 |
| Themes and Remaining Questions in Worm Wnt Signaling | 205 |
13. | The Wnt Gene Family and the Evolutionary Conservation of Wnt Expression | 210 |
| Abstract | 210 |
| Introduction | 210 |
| Recent Phylogenetic Analyses Fail to Resolve the Evolutionary History of the Wnt Gene Family | 211 |
| The Role of Wnt Genes in Establishing the Early Anteroposterior Axis in Deuterostomes | 212 |
| Echinoderms and Hemichordates | 213 |
| Ascidians | 215 |
| Amphioxus | 216 |
| Vertebrates | 218 |
| Evolutionary Conservation of Wnt Gene Involvement in Axial Patterning of Protostomes, Deuterostomes, and Cnidarians | 221 |
| Wnt Genes and Body Elongation from the Chordate Tail Bud | 222 |
| Conservation of Wnt Signaling in the Paraxial Mesoderm in Amphioxus and Vertebrates | 223 |
| The Roles of Wnt Genes in Patterning the Chordate Notochord | 225 |
| Is There an Evolutionary Conservation of Wnt Signaling in Segmentation between Chordates and Protostomes? | 225 |
| Evolutionary Conservation of the Roles of Wnt Genes in Convergent Extension and Planar Polarity Signaling | 226 |
| The Involvement of Wnt Genes in Patterning the Developing Central Nervous System | 227 |
| Conclusions | 228 |
14. | Wnt Signaling and Cell Migration | 240 |
| Abstract | 240 |
| Introduction | 240 |
| Wnt/Ca[superscript 2+]-Signaling Blocks Convergent Extension Movement | 243 |
| Wnt Signals Influence the Migrational Behavior of Myocytes | 247 |
| Perspectives | 248 |
15. | GSK3-Signal Regulation of Pattern Formation in Dictyostelium: Wnt-Like Pathways during Non-Canonical Multicellular Development | 251 |
| Abstract | 251 |
| Introduction | 251 |
| Antagonistic Regulation of Cell Fate Determination in Dictyostelium by the 7-Transmembrane cAMP Receptors CAR3 and CAR4 | 252 |
| GSK3, a Developmental Switch Regulating Anterior/Posterior Axis Formation | 253 |
| ZAK1 and PTPase Regulate Tyrosine Phosphorylation and Activity of GSK3 | 254 |
| Downstream Targets of GSK3 Aar ([beta]-Catenin) | 256 |
| Perspectives--Integrating Tyrosine Phosphorylation with Other Signaling Components | 258 |
| Index | 263 |