Development, Differentiation, and Disease of the Luminal Gastrointestinal Tract (eBook)

Front Cover 1
Progress In Molecular Biology and Translational Science: Development, Differentiation, and Disease of the Luminal Gastrointestinal Tract 4
Copyright 5
Contents 6
Contributors 12
Preface 14
Chapter 1: Formation of the Murine Endoderm 16
I. Introduction 17
II. Endoderm Morphogenesis 18
III. Molecular Control of Endoderm Formation 32
IV. Conclusions 41
References 42
Chapter 2: Dividing the Tubular Gut: Generation of Organ Boundaries at the Pylorus 50
I. Overview 51
II. Paths to the Pylorus Movements of Endodermal and Mesodermal Cells During Gut Tube Formation
III. Organ Formation in the Pyloric Domain 54
IV. Molecular Patterning of the Gut Tube: Establishing Stomach and Intestinal Domains 57
V. Establishing the Boundary Between Sox2- and Cdx2-Expressing Cells at the Pylorus 64
VI. Making the Pyloric Sphincter 66
VII. The Pylorus: A Compartment Boundary 69
Acknowledgments 72
References 72
Chapter 3: Molecular Determinants of Metaplastic and Neoplastic Transformation in the Esophageal Epithelium 78
I. Introduction 79
II. Esophageal Mucosal Homeostasis and Response to Injury-The Framework 79
III. Esophageal Mucosal Homeostasis-Molecular Determinants 84
IV. The Response to Injury, Metaplastic and Neoplastic Transformation in Esophagus-Molecular Derangements 86
V. Implications of Molecular Determinants, Derangements, and Future Research 99
References 100
Chapter 4: The Gastric Mucosa: Development and Differentiation 108
I. Introduction 109
II. Early Foregut Development 109
III. Specification of the Stomach as a Separate Organ: An Overview 110
IV. Morphogenetic Codes Involved in Stomach Specification 111
V. Transcription Factors 116
VI. Postnatal Gastric Development 119
VII. Adult Gastric Homeostasis 121
VIII. Morphogenetic Pathways in Maintaining Adult Gastric Homeostasis 124
IX. Concluding Remarks 125
Acknowledgment 126
References 126
Chapter 5: Oxyntic Atrophy, Metaplasia, and Gastric Cancer 132
I. Organization of the Normal Gastric Oxyntic Mucosa 133
II. The Development of Preneoplastic Metaplasia in the Stomach 133
III. Parietal Cell Loss Leads to Metaplasia in Mice 135
IV. What Factors Regulate the Induction of Metaplasia? 136
V. Cellular Origin of Metaplasia 137
VI. The Relationship of SPEM to Intestinal Metaplasia 138
VII. An Understanding of Metaplasia and the Development of Biomarkers for Preneoplasia 140
VIII. Future Directions for Understanding Metaplasia in the Stomach 142
Acknowledgments 142
References 142
Chapter 6: Hedgehog Signaling in Gastric Physiology and Cancer 148
I. Introduction 149
II. Hedgehog Gene Discovered in Mutagenesis Screens 149
III. Hh Ligands 150
IV. Regulation of Shh Gene Expression 151
V. Shh Processing 153
VI. Hh Receptors 154
VII. Primary Cilia and Hh Signaling 155
VIII. Hh Signaling and Gastric Physiology 157
Acknowledgments and Disclosures 165
References 165
Chapter 7: The Intestinal Stem Cell 172
I. Introduction 173
II. Monoclonality of Intestinal Crypts 174
III. The Identity and Localization of Intestinal Stem Cells 175
IV. Other Putative Intestinal Stem Cell Markers 177
V. The Intestinal Stem Cell Niche 178
VI. Evidence for a Nonmesenchymal Niche 183
VII. Intestinal Stem Cells as the Cell of Origin of Colorectal Cancer 184
VIII. Conclusion 185
References 185
Chapter 8: The Role of the Basement Membrane as a Modulator of Intestinal Epithelial-Mesenchymal Interactions 190
I. Introduction 191
II. Models of Epithelial-Mesenchymal Interactions in Developing Intestine 192
III. The Intestinal Basement Membrane 194
IV. Influence of the Extracellular Matrix in Epithelial Differentiation 199
V. Interplay between Basement Membrane Molecules and Transcription Factors 202
VI. Involvement of Basement Membrane Proteins at the Epithelial-Mesenchymal Interface in the Intestine: Use of Gene Ablation Models 207
VII. Genetic Inactivation of Laminin Receptors Leads to Intestinal Abnormalities 213
VIII. Conclusion and Future Directions 214
IX. Future Directions 215
Acknowledgments 215
References 216
Chapter 9: Regulation of Gene Expression in the Intestinal Epithelium 222
I. Introduction 223
II. Hedgehog Signaling 224
III. Forkhead Box Transcription Factors 225
IV. Homeobox Genes 228
V. Parahox Genes 228
VI. GATA Transcription Factors 230
VII. WNT Signaling 230
VIII. EPH/Ephrins 232
IX. SOX9 232
X. BMP Signaling 233
XI. PTEN/PI3K 234
XII. LKB1 Signaling 234
XIII. K-RAS 235
XIV. Notch Signaling 235
XV. HNF 236
XVI. MATH 1 237
XVII. Integration of Notch and WNT Signaling 237
XVIII. Emerging Mechanisms of Gene Regulation 237
Acknowledgments 239
References 239
Chapter 10: Cdx Genes, Inflammation, and the Pathogenesis of Intestinal Metaplasia 246
I. Introduction: Metaplasia, Dysplasia, and Transdifferentiation 247
II. The Cdx Genes and Their Roles During Normal Development 249
III. Intestinal Metaplasia is a Pathological Condition in Humans 252
IV. Chronic Gastric Inflammation Gives Rise to Gastric Intestinal Metaplasia (GIM) 254
V. Chronic Acid and Bile Reflux in the Esophagus Give Rise to Barrett's Esophagus 255
VI. Intestinal Metaplasia and Inflammation 258
VII. DNA Damage from Chronic Inflammation Promotes Metaplasia and Carcinogenesis 260
VIII. The Roles of Cdx1 and Cdx2 in H. pylori Induced GIM 262
IX. The Roles of Cdx1 and Cdx2 in GERD-Induced Barrett's Esophagus 266
X. Summary and Conclusions 273
References 274
Index 286