Development, Differentiation, and Disease of the Luminal Gastrointestinal Tract

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  • Edition: 1st
  • Format: Hardcover
  • Copyright: 2010-12-01

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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

Table of Contents

Contributorsp. xi
Prefacep. xiii
Formation of the Murine Endoderm: Lessons from the Mouse, Frog, Fish, and Chickp. 1
Introductionp. 2
Endoderm Morphogenesisp. 3
Molecular Control of Endoderm Formationp. 17
Conclusionsp. 26
Referencesp. 27
Dividing the Tubular Gut: Generation of Organ Boundaries at the Pylorusp. 35
Overviewp. 36
Paths to the Pylorus; Movements of Endodermal and Mesodermal Cells During Gut Tube Formationp. 38
Organ Formation in the Pyloric Domainp. 39
Molecular Patterning of the Gut Tube: Establishing Stomach and Intestinal Domainsp. 42
Establishing the Boundary Between Sox2- and Cdx2-Expressing Cells at the Pylorusp. 49
Making the Pyloric Sphincterp. 51
The Pylorus: A Compartment Boundaryp. 54
Referencesp. 57
Molecular Determinants of Metaplastic and Neoplastic Transformation in the Esophageal Epitheliump. 63
Introductionp. 64
Esophageal Mucosal Homeostasis and Response to Injury-The Frameworkp. 64
Esophageal Mucosal Homeostasis-Molecular Determinantsp. 69
The Response to Injury, Metaplastic and Neoplastic Transformation in Esophagus-Molecular Derangementsp. 71
Implications of Molecular Determinants, Derangements, and Future Researchp. 84
Referencesp. 85
The Gastric Mucosa: Development and Differentiationp. 93
Introductionp. 94
Early Foregut Developmentp. 94
Specification of the Stomach as a Separate Organ: An Overviewp. 95
Morphogenetic Codes Involved in Stomach Specificationp. 96
Transcription Factorsp. 101
Postnatal Gastric Developmentp. 104
Adult Gastric Homeostasisp. 106
Morphogenetic Pathways in Maintaining Adult Gastric Homeostasisp. 109
Concluding Remarksp. 110
Referencesp. 111
Oxyntic Atrophy, Metaplasia, and Gastric Cancerp. 117
Organization of the Normal Gastric Oxyntic Mucosap. 118
The Development of Preneoplastic Metaplasia in the Stomachp. 118
Parietal Cell Loss Leads to Metaplasia in Micep. 120
What Factors Regulate the Induction of Metaplasia?p. 121
Cellular Origin of Metaplasiap. 122
The Relationship of SPEM to Intestinal Metaplasiap. 123
An Understanding of Metaplasia and the Development of Biomarkers for Preneoplasiap. 125
Future Directions for Understanding Metaplasia in the Stomachp. 127
Referencesp. 127
Hedgehog Signaling in Gastric Physiology and Cancerp. 133
Introductionp. 134
Hedgehog Gene Discovered in Mutagenesis Screensp. 134
Hh Ligandsp. 135
Regulation of Shh Gene Expressionp. 136
Shh Processingp. 138
Hh Receptorsp. 139
Primary Cilia and Hh Signalingp. 140
Hh Signaling and Gastric Physiologyp. 142
Referencesp. 150
The Intestinal Stem Cellp. 157
Introductionp. 158
Monoclonality of Intestinal Cryptsp. 159
The Identity and Localization of Intestinal Stem Cellsp. 160
Other Putative Intestinal Stem Cell Markersp. 162
The Intestinal Stem Cell Nichep. 163
Evidence for a Nonmesenchymal Nichep. 168
Intestinal Stem Cells as the Cell of Origin of Colorectal Cancerp. 169
Conclusionp. 170
Referencesp. 170
The Role of the Basement Membrane as a Modulator of Intestinal Epithelial-Mesenchymal Interactionsp. 175
Introductionp. 176
Models of Epithelial-Mesenchymal Interactions in Developing Intestinep. 177
The Intestinal Basement Membranep. 179
Influence of the Extracellular Matrix in Epithelial Differentiationp. 184
Interplay Between Basement Membrane Molecules and Transcription Factorsp. 187
Involvement of Basement Membrane Proteins at the Epithelial-Mesenchymal Interface in the Intestine: Use of Gene Ablation Modelsp. 192
Genetic Inactivation of Laminin Receptors Leads to Intestinal Abnormalitiesp. 198
Conclusion and Future Directionsp. 199
Future Directionsp. 200
Referencesp. 201
Regulation of Gene Expression in the Intestinal Epitheliump. 207
Introductionp. 208
Hedgehog Signalingp. 209
Forkhead Box Transcription Factorsp. 210
Homeobox Genesp. 213
Parahox Genesp. 213
GATA Transcription Factorsp. 215
WNT Signalingp. 215
EPH/Ephrinsp. 217
SOX9p. 217
BMP Signalingp. 218
PTEN/PI3Kp. 219
LKB1 Signalingp. 219
K-RASp. 220
Notch Signalingp. 220
HNFp. 221
MATH 1p. 222
Integration of Notch and WNT Signalingp. 222
Emerging Mechanisms of Gene Regulationp. 222
Referencesp. 224
Cdx Genes, Inflammation, and the Pathogenesis of Intestinal Metaplasiap. 231
Introduction: Metaplasia, Dysplasia, and Transdifferentiationp. 232
The Cdx Genes and Their Roles During Normal Developmentp. 234
Intestinal Metaplasia is a Pathological Condition in Humansp. 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 Esophagusp. 240
Intestinal Metaplasia and Inflammationp. 243
DNA Damage from Chronic Inflammation Promotes Metaplasia and Carcinogenesisp. 245
The Roles of Cd×1 and Cd×2 in H. pylori Induced GIMp. 247
The Roles of Cd×1 and Cd×2 in GERD-Induced Barrett's Esophagusp. 251
Summary and Conclusionsp. 258
Referencesp. 259
Indexp. 271
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