Development, Differentiation, and Disease of the Luminal Gastrointestinal Tract

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ISBN: 9780123812803 | 0123812801
Cover: Hardcover
Copyright: 12/2/2010

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Understanding how digestive organs develop, their physiology and structure is important for determining new therapies to combat diseases of the digestive organs. This volume reviews the latest research and developments in this field.* Discusses new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Contributors	p. xi
Preface	p. xiii
Formation of the Murine Endoderm: Lessons from the Mouse, Frog, Fish, and Chick	p. 1
Introduction	p. 2
Endoderm Morphogenesis	p. 3
Molecular Control of Endoderm Formation	p. 17
Conclusions	p. 26
References	p. 27
Dividing the Tubular Gut: Generation of Organ Boundaries at the Pylorus	p. 35
Overview	p. 36
Paths to the Pylorus; Movements of Endodermal and Mesodermal Cells During Gut Tube Formation	p. 38
Organ Formation in the Pyloric Domain	p. 39
Molecular Patterning of the Gut Tube: Establishing Stomach and Intestinal Domains	p. 42
Establishing the Boundary Between Sox2- and Cdx2-Expressing Cells at the Pylorus	p. 49
Making the Pyloric Sphincter	p. 51
The Pylorus: A Compartment Boundary	p. 54
References	p. 57
Molecular Determinants of Metaplastic and Neoplastic Transformation in the Esophageal Epithelium	p. 63
Introduction	p. 64
Esophageal Mucosal Homeostasis and Response to Injury-The Framework	p. 64
Esophageal Mucosal Homeostasis-Molecular Determinants	p. 69
The Response to Injury, Metaplastic and Neoplastic Transformation in Esophagus-Molecular Derangements	p. 71
Implications of Molecular Determinants, Derangements, and Future Research	p. 84
References	p. 85
The Gastric Mucosa: Development and Differentiation	p. 93
Introduction	p. 94
Early Foregut Development	p. 94
Specification of the Stomach as a Separate Organ: An Overview	p. 95
Morphogenetic Codes Involved in Stomach Specification	p. 96
Transcription Factors	p. 101
Postnatal Gastric Development	p. 104
Adult Gastric Homeostasis	p. 106
Morphogenetic Pathways in Maintaining Adult Gastric Homeostasis	p. 109
Concluding Remarks	p. 110
References	p. 111
Oxyntic Atrophy, Metaplasia, and Gastric Cancer	p. 117
Organization of the Normal Gastric Oxyntic Mucosa	p. 118
The Development of Preneoplastic Metaplasia in the Stomach	p. 118
Parietal Cell Loss Leads to Metaplasia in Mice	p. 120
What Factors Regulate the Induction of Metaplasia?	p. 121
Cellular Origin of Metaplasia	p. 122
The Relationship of SPEM to Intestinal Metaplasia	p. 123
An Understanding of Metaplasia and the Development of Biomarkers for Preneoplasia	p. 125
Future Directions for Understanding Metaplasia in the Stomach	p. 127
References	p. 127
Hedgehog Signaling in Gastric Physiology and Cancer	p. 133
Introduction	p. 134
Hedgehog Gene Discovered in Mutagenesis Screens	p. 134
Hh Ligands	p. 135
Regulation of Shh Gene Expression	p. 136
Shh Processing	p. 138
Hh Receptors	p. 139
Primary Cilia and Hh Signaling	p. 140
Hh Signaling and Gastric Physiology	p. 142
References	p. 150
The Intestinal Stem Cell	p. 157
Introduction	p. 158
Monoclonality of Intestinal Crypts	p. 159
The Identity and Localization of Intestinal Stem Cells	p. 160
Other Putative Intestinal Stem Cell Markers	p. 162
The Intestinal Stem Cell Niche	p. 163
Evidence for a Nonmesenchymal Niche	p. 168
Intestinal Stem Cells as the Cell of Origin of Colorectal Cancer	p. 169
Conclusion	p. 170
References	p. 170
The Role of the Basement Membrane as a Modulator of Intestinal Epithelial-Mesenchymal Interactions	p. 175
Introduction	p. 176
Models of Epithelial-Mesenchymal Interactions in Developing Intestine	p. 177
The Intestinal Basement Membrane	p. 179
Influence of the Extracellular Matrix in Epithelial Differentiation	p. 184
Interplay Between Basement Membrane Molecules and Transcription Factors	p. 187
Involvement of Basement Membrane Proteins at the Epithelial-Mesenchymal Interface in the Intestine: Use of Gene Ablation Models	p. 192
Genetic Inactivation of Laminin Receptors Leads to Intestinal Abnormalities	p. 198
Conclusion and Future Directions	p. 199
Future Directions	p. 200
References	p. 201
Regulation of Gene Expression in the Intestinal Epithelium	p. 207
Introduction	p. 208
Hedgehog Signaling	p. 209
Forkhead Box Transcription Factors	p. 210
Homeobox Genes	p. 213
Parahox Genes	p. 213
GATA Transcription Factors	p. 215
WNT Signaling	p. 215
EPH/Ephrins	p. 217
SOX9	p. 217
BMP Signaling	p. 218
PTEN/PI3K	p. 219
LKB1 Signaling	p. 219
K-RAS	p. 220
Notch Signaling	p. 220
HNF	p. 221
MATH 1	p. 222
Integration of Notch and WNT Signaling	p. 222
Emerging Mechanisms of Gene Regulation	p. 222
References	p. 224
Cdx Genes, Inflammation, and the Pathogenesis of Intestinal Metaplasia	p. 231
Introduction: Metaplasia, Dysplasia, and Transdifferentiation	p. 232
The Cdx Genes and Their Roles During Normal Development	p. 234
Intestinal Metaplasia is a Pathological Condition in Humans	p. 237
Chronic Gastric Inflammation Gives Rise to Gastric Intestinal Metaplasia (GIM)	p. 239
Chronic Acid and Bile Reflux in the Esophagus Give Rise to Barrett's Esophagus	p. 240
Intestinal Metaplasia and Inflammation	p. 243
DNA Damage from Chronic Inflammation Promotes Metaplasia and Carcinogenesis	p. 245
The Roles of Cd×1 and Cd×2 in H. pylori Induced GIM	p. 247
The Roles of Cd×1 and Cd×2 in GERD-Induced Barrett's Esophagus	p. 251
Summary and Conclusions	p. 258
References	p. 259
Index	p. 271
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Development, Differentiation, and Disease of the Luminal Gastrointestinal Tract

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