Note: Intro -- Title Page -- Copyright Page -- DEDICATION -- PREFACE -- ABOUT THE EDITORS... -- PARTICIPANTS -- Table of Contents -- CHAPTER 1 THE MOLECULAR BASIS OF NOTCH SIGNALING: A Brief Overview -- INTRODUCTION -- BASIC MECHANISMS OF NOTCH SIGNALING PATHWAYS -- MODULATION OF NOTCH SIGNAL TRANSDUCTION -- NOTCH SIGNALING IN VASCULAR DEVELOPMENT -- NOTCH SIGNALING IN CANCER DEVELOPMENT -- NOTCH IN SOLID TUMORS -- NOTCH SIGNALING IN EMBRYONIC DEVELOPMENT -- ORIGINS OF ROLES FOR NOTCH SIGNALING IN EARLY EMBRYOGENESIS -- NOTCH SIGNALING IS OFTEN INVOLVED IN MESODERM FORMATION -- CONCLUSION -- REFERENCES -- CHAPTER 2 THE ROLE OF ADAMS IN NOTCH SIGNALING -- INTRODUCTION -- NOTCH SIGNALING -- NOTCH PROTEOLYSIS SITE-1 (S1, FURIN, SERINE PROTEASE) -- SITE-2 (S2, ADAM10, METALLOPROTEASE) -- SITE-3 (S3, PRESENILIN, ASPARTYL PROTEASE) -- THE ADAM FAMILY OF PROTEASES -- NOTCH RECEPTOR CLEAVAGE BY ADAMs -- NOTCH LIGAND CLEAVAGE BY ADAMS -- NOTCH S2-PROTECTION FROM RIP -- SUBSTRATE REQUIREMENTS FOR S2 -- LOCATION OF S2 CLEAVAGE -- TARGETING S2 PROTEOLYSIS IN CANCER -- CONCLUSION -- WEB LINKS -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 3 METABOLISM AND TRANSPORTATION PATHWAYS OF GDP-FUCOSE THAT ARE REQUIRED FOR THE O-FUCOSYLATION OF NOTCH -- INTRODUCTION -- PROPER STRUCTURE OF ITS EXTRACELLULAR DOMAIN IS CRUCIAL FOR THE ACTIVATION OF NOTCH -- MODIFICATIONS OF O-LINKED GLYCANS IN THE EGF-LIKE REPEATS OF NOTCH -- THE MONOSACCHARIDE O-FUCOSE MODIFICATION ON THE EGF-LIKE REPEATS OF NOTCH DOES NOT HAVE A MAJOR ROLE IN NOTCH SIGNALING -- METABOLIC PATHWAY FOR THE O-FUCOSE MODIFICATION OF NOTCH EGF-LIKE REPEATS -- INTRACELLULAR TRANSPORTATION OF GDP-FUCOSE IS CRUCIAL FOR THE O-FUCOSYLATION OF NOTCH EGF-LIKE REPEATS -- A REDUCTION IN NOTCH SIGNALING ACTIVITY MAY ACCOUNT FOR THE PATHOLOGY OF CDG IIC. , MECHANISMS REQUIRED FOR THE INTRACELLULAR SUPPLY OF GDP-FUCOSE FOR THE O-FUCOSYLATION OF THE NOTCH EGF-LIKE REPEATS -- CONCLUSION -- REFERENCES -- CHAPTER 4 NOTCH SIGNALING AND THE GENERATION OF CELL DIVERSITY IN DROSOPHILA NEUROBLAST LINEAGES -- INTRODUCTION -- NOTCH IS REQUIRED FOR LATERAL INHIBITION DURING THE PHASE OF NEURAL STEM CELL GENERATION -- ASYMMETRIC CELL DIVISION AS A MECHANISM TO GENERATE CELL DIVERSITY IN NEUROBLAST LINEAGES -- FUNCTION OF NOTCH IN BINARY CELL FATE SPECIFICATION IN THE DROSOPHILA NERVOUS SYSTEM -- NOTCH FUNCTION IN CELL FATE SPECIFICATION IN THE EMBRYONIC NB7-3 LINEAGE -- NOTCH FUNCTION DURING LARVAL NEUROGENESIS -- Is There Contextual Control of Notch Activity? -- DOWN-STREAM NOTCH TARGETS/EFFECTORS -- Is Notch Instructive or Permissive? -- CONCLUSION -- ACKNOWLEDGEMENT -- REFERENCES -- CHAPTER 5 NEPRO: A Novel Notch Effector for Maintenance of Neural Progenitor Cells in the Neocortex -- INTRODUCTION -- THE NOTCH PATHWAY IS ESSENTIAL FOR MAINTENANCE OF NPCs -- IDENTIFICATION OF NEPRO -- NEPRO INHIBITS NEURONAL DIFFERENTIATION AND IS NECESSARY FOR THE MAINTENANCE OF NPCs -- NEPRO IS IN PARALLEL WITH HES, DOWNSTREAM OF NOTCH -- NEPRO IS AN ESSENTIAL EFFECTOR FOR THE NOTCH PATHWAY -- DISCUSSION -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 6 NOTCH SIGNALING AND DEVELOPMENT OF THE HEMATOPOIETIC SYSTEM -- INTRODUCTION -- OVERVIEW OF NOTCH SIGNALING -- NOTCH AND EMERGENCE OF DEFINITIVE HEMATOPOIETIC STEM CELLS -- NOTCH AND MAINTENANCE OF HEMATOPOIETIC STEM CELLS -- NOTCH AND T-CELL DEVELOPMENT -- OTHER FUNCTIONS OF NOTCH IN HEMATOPOIESIS -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 7 NOTCH SIGNALING IN LUNG DEVELOPMENT AND DISEASE -- INTRODUCTION -- NOTCH PROMOTES PROXIMAL CELL FATES IN EARLY LUNG DEVELOPMENT -- NOTCH COORDINATES ALVEOLAR DEVELOPMENT. , THE ROLE OF NOTCH IN REPAIR AND DISEASE OF THE ADULT LUNG -- NOTCH AND LUNG CANCER -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 8 THE ROLE OF NOTCH SIGNALING IN KIDNEY DEVELOPMENT AND DISEASE -- INTRODUCTION -- NOTCH SIGNALING IN PRONEPHROS DEVELOPMENT -- NOTCH SIGNALING IN METANEPHROS DEVELOPMENT -- An Overview of Metanephros Development -- Notch Signaling in the Developing Mammalian Nephron -- Notch Signaling in Collecting Duct Development -- NOTCH SIGNALING IN KIDNEY DISEASES AND RENAL EPITHELIAL CANCERS -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 9 NOTCH SIGNALING AND THE DEVELOPING SKELETON -- INTRODUCTION -- Notch Pathway Regulation of Somitogenesis -- Notch Signaling Initiates Chondrogenesis while Repressing Differentiation -- Notch Inhibition of Osteoblast Differentiation -- Notch Pathway Suppression of Osteoclastogenesis -- NOTCH PATHWAY ASSOCIATED SKELETAL DISORDERS -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 10 NOTCH SIGNALING AND THE DEVELOPING SKIN EPIDERMIS -- INTRODUCTION -- NOTCH SIGNALING -- LOCALIZATION OF NOTCH RECEPTORS AND LIGANDS IN EPIDERMIS -- GROWTH ARREST AND ADHESION -- NOTCH AND TERMINAL DIFFERENTIATION -- DELETION OR ACTIVATION OF NOTCH PATHWAY COMPONENTS -- CROSS-TALKS WITH OTHER PATHWAYS -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 11 NOTCH SIGNALING AND THE DEVELOPING HAIR FOLLICLE -- INTRODUCTION -- DEVELOPMENT AND STRUCTURE OF THE HAIR FOLLICLE -- EXPRESSION OF MEMBERS OF THE NOTCH PATHWAY IN THE HAIR FOLLICLE -- Expression during Embryogenesis -- Expression during Postnatal Life -- NO ESSENTIAL ROLE FOR NOTCH IN THE INITIAL STEPS OF EMBRYONIC HAIR FOLLICLE DEVELOPMENT -- NOTCH AND THE MAINTENANCE OF CELLULAR IDENTITY WITHIN THE HAIR FOLLICLE -- Gain of Function Mutations in Notch Pathway Act Non Cell Autonomously on Hair Follicle Differentiation. , Loss of Notch Function in Hair Follicles Leads to Alopecia and/or Alteration in the Differentiation Program -- NOTCH AND THE REGULATION OF CELL FATE IN HAIR FOLLICLES -- ADDITIONAL ROLES FOR NOTCH IN HAIR FOLLICLES -- Control of Hair Follicle Cycling -- Control of Cell Proliferation and Apoptosis in Hair Bulbs -- Development of Sebaceous Glands -- Melanocyte Homeostasis -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 12 NOTCH SIGNALING AND THE DEVELOPING INNER EAR -- INTRODUCTION: STRUCTURE AND DEVELOPMENT OF MAMMALIAN INNER EAR -- MULTIPLE ROLES OF NOTCH SIGNALING PATHWAY DURING INNER EAR DEVELOPMENT -- Hair Cell and Supporting Cell Differentiation -- Determination of Prosensory Region -- Jagged1 and Prosensory Determination -- Role of Notch Signaling in Induction for Prosensory Region -- Possible Effectors of the Notch Signaling Pathway in the Context of Early Prosensory Formation -- Biphasic Regulation of Cell Proliferation by the Notch Signaling Pathway during the Inner Ear Development -- Delamination of Neural Progenitors -- NOTCH SIGNALING PATHWAY AND THE INNER EAR REGENERATION -- CONCLUSION -- REFERENCES -- CHAPTER 13 NOTCH SIGNALING IN CANCER STEM CELLS -- INTRODUCTION -- THE CANCER STEM CELL MODEL -- CLINICAL IMPLICATIONS OF CANCER STEM CELLS -- CANCER STEM CELLS AND CHEMORESISTANCE -- CANCER STEM CELLS AND RADIORESISTANCE -- NOTCH SIGNALING IN CANCER STEM CELLS -- NOTCH PROTECTS CANCER STEM CELLS FROM RADIATION -- CONCLUSION -- REFERENCES -- CHAPTER 14 NOTCH SIGNALING PATHWAY AND CANCER METASTASIS -- INTRODUCTION -- CRITICAL CELLULAR AND MOLECULAR EVENTS IN CANCER METASTASIS -- EMT and Cancer Cell Dissemination -- Invasion and Cell Migration -- Resistances to Apoptosis and Anoikis -- Angiogenesis and Lymphangiogenesis -- The "Seed and Soil Hypothesis" -- Metastatic Cancer Stem Cells (CSCs) -- THE NOTCH SIGNALING PATHWAY. , The Components of the Notch Signaling Pathway -- The Regulation of the Notch Signaling Pathway -- NOTCH SIGNALING PATHWAY AND CANCER METASTASIS -- Osteosarcoma -- Breast Cancer -- Prostate Cancer -- Melanoma -- THE MECHANISMS OF NOTCH FUNCTION ON CANCER METASTASIS -- Notch Signaling Converts the Hypoxic Stimulus into EMT -- Blocking Notch Signaling Produces Dysfunctional Tumor Vessels -- Notch Signaling Promotes Anoikis-Resistance of Tumor Cells -- CONCLUSION -- ACKNOWLEDGEMENT -- REFERENCES -- CHAPTER 15 NOTCH, APOPTOSIS AND CANCER -- INTRODUCTION -- p53 PATHWAY -- NF-kB PATHWAY AND NOTCH IN APOPTOSIS -- PI3K-Akt PATHWAY -- NOTCH AND THE MAJOR APOPTOTIC PATHWAYS -- CONCLUSION -- REFERENCES -- CHAPTER 16 LIGAND-DEPENDENT NOTCH SIGNALING IN VASCULAR FORMATION -- INTRODUCTION -- BASIC MECHANISMS OF THE NOTCH RECEPTOR LIGAND-SIGNALING PATHWAY -- NOTCH RECEPTOR AND LIGAND EXPRESSION IN BLOOD VESSELS -- NOTCH1, NOTCH4 AND THE LIGANDS DIII AND DII4 DURING ARTERIAL SPECIFICATION AND MAINTENANCE -- NOTCH3, JAGGED1 AND Dll1 DURING SMOOTH-MUSCLE DIFFERENTIATION AND MATURATION -- DII4 AND JAGGED1 IN TIP- AND STALK-CELL SPECIFICATION DURING SPROUTING ANGIOGENESIS -- NOTCH LIGANDS IN PATHOLOGICAL ANGIOGENESIS -- NOTCH SIGNALING IN PERIPHERAL ISCHEMIA -- CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- CHAPTER 17 NOTCH AND THE p53 CLAN OF TRANSCRIPTION FACTORS -- INTRODUCTION -- NOTCH -- THE p53 CLAN -- CROSSTALK OF NOTCH WITH THE p53 CLAN IN DEVELOPMENT, DIFFERENTIATION AND HOMEOSTASIS -- CROSSTALK OF NOTCH WITH THE p53 CLAN IN CANCER AND OTHER DISEASES -- CONCLUSION -- REFERENCES -- CHAPTER 18 NOTCH SIGNALING AND BREAST CANCER -- INTRODUCTION -- EVIDENCE FOR ONCOGENIC NOTCH IN CARCINOMA OF THE BREAST -- MECHANISMS OF NOTCH ACTIVATION IN BREAST CANCER -- MECHANISMS OF NOTCH-INDUCED TRANSFORMATION -- Notch in Mammary Stem Cells and Tumor Initiating Cells. , Notch, Lineage Specification and Breast Cancer Subtype.

Note: Intro -- Preface -- Contents -- Contributors -- About the Editors -- Chapter 1: Notch Signaling and Tissue Patterning in Embryology: An Introduction -- References -- Chapter 2: Notch Signaling and Embryonic Development: An Ancient Friend, Revisited -- Introduction -- Challenge and Promise: The Impact of Notch Signaling for the Embryogenesis of the Central Nervous System (CNS) -- Embryogenesis of the Central Nervous System (CNS): A Brief Introduction -- Embryonic Neural Stem Cells and Notch Signaling -- Unraveling Hidden Secrets: Notch Signaling in the Embryonic Development of Skin and Hair Follicles -- From the Bench to the Patient: The Impact of the Notch Pathway for Embryonic Kidney Development, Notch2, Jag1, and Beyond -- Notch Receptor 2 and Its Corresponding Ligand Jag1 Are Key Players for Embryonic Liver Development -- The Role of Notch Signaling for Embryonic Development of the Pancreas -- Notch2 and Jag1 Function in Embryonic Heart Development -- Notch2 and Jag1 Function During Skeletal Development -- The Impact of the Notch Pathway for Angiogenesis -- Roles for Notch2 and Jag1 in the Embryonic Development of Inner Ear and Eye, Tissues with Important Sensory Functions -- Conclusions -- References -- Chapter 3: The Five Faces of Notch Signalling During Drosophila melanogaster Embryonic CNS Development -- Introduction -- Notch Canonical Molecular Pathway -- Notch Non-canonical Molecular Pathway -- Neuroblast Selection and Delamination -- The Type I-> -- 0 Daughter Cell Proliferation Switch -- Dictating Asymmetric Cell Fate Between Sibling Neurons -- Glia Development -- Axon Pathfinding -- Conclusions -- References -- Chapter 4: Epigenetic Regulation of Notch Signaling During Drosophila Development -- Introduction -- Notch Signaling -- The Advantages of Drosophila as Model Organism for Notch Signaling Study. , The Chromatin Assembly Factor CAF-1 -- Epigenetic Regulation of Notch Signaling by CAF-1 -- Epigenetic Regulation of Notch Signaling by Other Epigenetic Regulators -- Conclusion -- References -- Chapter 5: Regulation of Proneural Wave Propagation Through a Combination of Notch-Mediated Lateral Inhibition and EGF-Mediated Reaction Diffusion -- The Proneural Wave -- The Link Between Proneural Transcription Factors and Notch Signaling -- The Link Between Proneural Transcription Factors and EGF Signaling -- Establishing a Mathematical Model of the Proneural Wave -- Phenomenological Versus Mechanistic Models -- The Mathematical Model Reproduces the Essential Behaviors of the Proneural Wave -- Two Distinct Functions of Notch Signaling -- Using the Model to Solve the Paradox of the Notch Mutant Phenotype -- Expanding the Roles of Notch to Other Biological Phenomena -- References -- Chapter 6: A Nucleolar Protein, Nepro, Is Essential for the Maintenance of Early Neural Stem Cells and Preimplantation Embryos -- Development of the Neocortex -- Notch Signaling Is Required for the Maintenance of NSCs -- Both Nepro and Hes Are Required for the Maintenance of Early NSCs -- Nepro Is also Required for the Maintenance of the Preimplantation Embryo -- Notch Signaling Controls Dendritic Complexity of Mitral Cells in the Olfactory Bulb -- Discussion -- Conclusion -- References -- Chapter 7: Role of Notch Signaling in Leg Development in Drosophila melanogaster -- Introduction -- Leg Segmentation and Positioning of Notch Activity -- Leg Specification and Proximo-distal Patterning -- Segmentation of the Tarsal Region -- Dl/Ser Positioning and Notch Activation -- Notch Regulation of Leg Development -- Joint Formation in Response to Notch Activity -- Dysfusion Control of Tarsal Joint Morphogenesis. , Localized Apical Constriction Drives Epithelial Folding to Form the Tarsal Joints -- Dysf-Dependent Rho1 Activity Regulates Apical Constriction -- Dysf Transcriptional Control of Apical Constriction -- Adult Joint Formation Depends on Notch Activity -- Notch Regulation of Leg Growth -- References -- Chapter 8: Notch Signalling: The Multitask Manager of Inner Ear Development and Regeneration -- Introduction -- The Notch Signalling Pathway -- Introduction to the Inner Ear -- Roles of Notch During Inner Ear Development -- Lateral Inhibition and the Regulation of Otic Neurogenesis -- Lateral Inhibition and Hair Cell Fate Decisions -- Lateral Induction and Prosensory Specification -- Notch Signalling During Otic Placode Formation -- Managing and Multitasking: Specificity and Integration of Notch Functions in the Developing Inner Ear -- Competence States Determine the Context-Specific Effects of Notch Signalling -- Integration of Notch Activity from Multiple Ligands and Modes of Signalling -- Integration of Notch Signalling with Cell Proliferation and Rearrangements -- Notch Signalling and Hair Cell Regeneration -- Conclusion -- References -- Chapter 9: Notch Pathway and Inherited Diseases: Challenge and Promise -- Introduction -- Defective Notch Signaling and Embryogenesis: Congenital Heart Disease (CHD) as an Example for the Broad Variety of Pathophysiological Consequences in Individual Tissues -- Alagille Syndrome (ALGS) -- Molecular Biology and Genetics of Alagille Syndrome (ALGS) -- Clinical Hallmarks of Alagille Syndrome -- Adams-Oliver Syndrome: Highlighting the Impact of NOTCH1, DLL4, and RBPJk for Human Embryogenesis -- Historical Considerations -- Molecular Biology and Genetics of Adams-Oliver Syndrome -- Clinical Findings in Adams-Oliver Syndrome -- Hajdu-Cheney Syndrome (HCS) (OMIN 102500) -- Historical Considerations. , Molecular Biology and Genetics of Hajdu-Cheney Syndrome (HCS) -- Clinical Findings in Hajdu-Cheney Syndrome (HCS) -- Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) (OMIM 125310) -- Early-Onset Arteriopathy with Cavitating Leukodystrophy (EACL) -- Lateral Meningocele Syndrome (LMS) (OMIM 130720) -- Infantile Myofibromatosis-2 (IM-2) (OMIM 615293) -- Conclusions -- References -- Index.