Hedgehog-gli signaling in human disease / Ariel Ruiz i Altaba.

Format:

Book

Author/Creator:

Ruiz i Altaba, Ariel.

Series:

Molecular biology intelligence unit (Unnumbered)

Molecular biology intelligence unit

Language:

English

Subjects (All):

Cellular signal transduction.

Oncogenes.

Tumor proteins.

Signal Transduction--physiology.

Oncogene Proteins--metabolism.

Transcription Factors--metabolism.

Medical Subjects:

Signal Transduction--physiology.

Oncogene Proteins--metabolism.

Transcription Factors--metabolism.

Physical Description:

228 pages : illustrations (some color) ; 24 cm.

Place of Publication:

Georgetown, Tex. : Landes Bioscience/Eurekah.com ; New York, N.Y. : Springer Science+Business Media, [2006]

Summary:

Hedgehog-GLI Signaling in Human Disease represents the first compilation of up-to-date reviews by top-level scientists in this important field of research. The chapters cover a wide spectrum of related interests, from the molecular bases of morphogen function, to human genetics to cancer research. The aim of the book is to disseminate information on this exciting field, to allow students, scientists and the public in general to gain access current information from research leaders and to provide a book that encompasses different aspects of research showing the fusion of basic research in model systems and medicine. This is a timely primer on how a system of cell communication, Hedgehog-GLI signaling, plays a critical role in human disease and thus provides the background for the development of novel and rational therapies.

Contents:

1 How the Hedgehog Outfoxed the Crab: Interference with Hedgehog-Gli Signaling as Anti-Cancer Therapy? / Ariel Ruiz I Altaba 1

2 The Patched Receptor: Switching On/Off the Hedgehog Signaling Pathway / Luis Quijada, Ainhoa Callejo, Carlos Torroja, Isabel Guerrero 23

The Hedgehog Signaling Pathway 23

Sequence and Functional Analysis of Ptc 25

Hedgehog Lipid Modifications and Morphogen Distribution 25

Reception of Hh 26

Hh Internalization and Signal Transduction 26

Smo Regulation by Ptc 27

Ptc and Human Disease 28

3 Making a Morphogenetic Gradient / Henk Roelink 34

Disp 1, A Molecule Dedicated to the Export of Shh 35

Is Shh Handed Over from Cell to Cell Using an Active Mechanism? 38

4 Spatial and Temporal Regulation of Hair Follicle Progenitors by Hedgehog Signaling / Anthony E. Oro 41

The Hair Follicle Cycle 43

Interfollicular Epithelial Cells Are Competent to Induce Shh Target Genes 43

Outcomes of Shh Target Gene Induction in the Skin 46

Regulation of Shh Induction in a Multipotent Epithelium 47

Regulation of Shh Signal Reception 47

Maintenance of Shh Signaling during Tissue Morphogenesis 49

Future Perspectives 49

5 Mode of PTCH1/Ptch1-Associated Tumor Formation: Insights from Mutant Ptch1 Mice / Heidi Hahn 53

Is Loss of Both PTCH1/Ptch1 Alleles Required for Tumor Formation? 55

What Are the Modifiers of PTCH1/Ptch1-Associated Tumorigenesis? 58

6 Basal Cell Carcinomas, Hedgehog Signaling, and the Ptch1+/- Mouse / Ervin Epstein, Jr. 63

Rhabdomyosarcomas 65

Medulloblastomas 65

BCCs 66

7 Gli genes and Their Targets in Epidermal Development and Disease / Fritz Aberger, Anna-Maria Frischauf 74

Gli Genes and Epidermal Development 75

Human Epidermis and the Origin of BCC 77

Gli1 and Gli2 in Basal Cell Carcinoma 80

The Oncogenic Nature of Gli Transcription Factors 80

Regulation of Gli Expression 82

Unresolved Problems and Future Perspectives 82

8 Splitting Hairs: Dissecting the Roles of Gli Activator and Repressor Functions during Epidermal Development and Disease / Pleasantine Mill, Chi-Chung Hui 86

The Gli Family of Transcription Factors in Hh Signaling 86

Molecular Mechanisms of Embryonic and Adult Hair Development 95

Shh: Stem Cells, Cell Cycle and Cancer 101

9 Shh Expression in Pulmonary Injury and Disease / Paul M. Fitch, Sonia J. Wakelin, Jacqueline A. Lowrey, William A.H. Wallace, Sarah E.M. Howie 119

The Hedgehog Pathway 119

Hedgehog Signalling in Normal Pulmonary Tissues 120

Hedgehog Signalling in Injury and Disease 120

Shh in the Immune System 123

Hedgehogs and Pulmonary Progenitor Cells 124

Shh and Type II Epithelial Cells 125

10 Human Correlates of Gli3 Function / Leslie G. Biesecker 129

The Delineation of the Greig Cephalopolysyndactyly Syndrome (GCPS) 129

The Molecular Basis of GCPS 130

The Clinical Delineation of Pallister-Hall Syndrome (PHS) 130

Animal Models of Gli3 Phenotypes 131

11 From Oligodactyly to Polydactyly: Role of Shh and Gli3 in Limb Morphogenesis / Chin Chiang 137

Shh Expression and the Specification of Digit Identity 138

Congenital Limb Malformations Associated with Shh Misregulation 139

Shh Activity in Limb Patterning Is Mediated by Gli3 141

Congenital Limb Malformations Are Associated with Gli3 Mutations 142

12 The Genetics of Indian Hedgehog / M. Elizabeth McCready, Dennis E. Bulman 146

Brachydactyly Type A1 147

Acrocapitofemoral Dysplasia (ACFD) 149

Comparison of Humann IHH Disorders 149

IHH Animal Model 150

13 Sonic Hedgehog Signaling in Craniofacial Development / Dwight Cordero, Minal Tapadia, Jill A. Helms 153

The Face in Myth and Reality 153

The Craniofacial Consequences of Disrupting SHH Signaling: The Human Experience 156

Models to Study Craniofacial Development 158

Craniofacial Consequences of Shh Perturbation: The Model Experience 158

Embryologic Aspects of Normal Craniofacial Development: An Introduction 161

Future Directions 171

14 Important Role of Shh Controlling Gli3 Functions during the Dorsal-Ventral Patterning of the Telencephalon / Jun Motoyama, Kazushi Aoto 177

Shh Signaling and Dorsal-Ventral Patterning of the Telencephalon 177

Gli3 as an Activator of Dorsal Cell Types 182

Gli3 as a Suppressor of Ventral Cell Type 182

Importance of the Balance between Gli3 and Shh 183

Future Perspectives 183

15 Regulation of Early Events in Cell Cycle Progression by Hedgehog Signaling in CNS Development and Tumorigenesis / Anna Marie Kenney, David H. Rowitch 187

Mitogenic Signaling in the Developing CNS 187

SHH Signaling Is Required for Growth of Cerebellar Granule Neuron Precursors and Is Etiologic in Medulloblastoma 193

N-MYC as a Key Component of Hh Signaling 197

16 Modulating the Hedgehog Pathway in Diseases / Frederic J. de Sauvage, Lee L. Rubin 210

Identification of Small Molecule Hedgehog (Hh) Antagonists 211

Identification of Hh Small Molecule Hh Agonists 212

17 Hedgehog Signaling in Endodermally Derived Tumors / Marina Pasca di Magliano, Matthias Hebrok 215

The Hedgehog Signaling Pathway 215

Hedgehog Signaling in Gastrointestinal Tumors of the Pancreas and Colon 218.

Notes:

Includes bibliographical references and index.

ISBN:

0387257845

9780387257846

OCLC:

61860815

Online:

Publisher description