Wnt Signaling in Development and Disease Molecular Mechanisms and Biological Functions

About this book

Widely recognized as one of the most important signaling mechanisms in development and disease, Wnt signaling pathways are networks of proteins that play significant roles in embryogenesis or cancer development. Wnt Signaling in Development and Disease addresses the fundamentals of Wnt signaling and delves into molecular pathway mechanisms, its role in embryogenesis, adult tissue homeostasis, and chronic disease. This comprehensive resource details current knowledge of Wnt signaling while looking ahead to future progress.

Contents

Contributors vii

Preface xi

Part 1 Molecular Signaling Mechanisms: From Pathways to Networks 1

1 Wnt Signal Production, Secretion, and Diffusion 3
Madelon M. Maurice and Hendrik C. Korswagen

2 Wnt Signaling at the Membrane 15
Gary Davidson and Christof Niehrs

3 Wnt Signal Transduction in the Cytoplasm: an Introduction to the Destruction Complex 33
Tony W. Chen, Heather A. Wallace, Yashi Ahmed, and Ethan Lee

4 An Overview of Gene Regulation by Wnt/?-Catenin Signaling 51
Chen U. Zhang and Ken M. Cadigan

5 Finding a Needle in a Genomic Haystack: Genome-Wide Approaches to Identify Wnt/TCF Transcriptional Targets 73
Chandan Bhambhani and Ken M. Cadigan

6 Introduction to ?-Catenin-Independent Wnt Signaling Pathways 89
Susanne Kühl and Michael Kühl

7 Molecular Mechanisms of Wnt Pathway Specificity 101
Alexandra Schambony, Guido J.R. Zaman, and Folkert Verkaar

8 Modulation of Wnt Signaling by Endocytosis of Receptor Complexes 113
Akira Kikuchi, Shinji Matsumoto, Katsumi Fumoto, and Akira Sato

9 New Insights from Proteomic Analysis of Wnt Signaling 125
Matthew P. Walker, Dennis Goldfarb, and Michael B. Major

10 New Insights about Wnt/?-Catenin Pathway Mechanisms from Global siRNA Screens 137
Tenzin Gocha and Ramanuj DasGupta

11 Mathematical Models of Wnt Signaling Pathways 153
Michael Kühl, Barbara Kracher, Alexander Groß, and Hans A. Kestler

12 The Wnt’s Tale: On the Evolution of a Signaling Pathway 161
Jenifer C. Croce and Thomas W. Holstein

Part 2 Selected Key Molecules in Wnt Signaling 177

13 Secreted Wnt Inhibitors or Modulators 179
Paola Bovolenta, Anne-Kathrin Gorny, Pilar Esteve, and Herbert Steinbeisser

14 Frizzleds as G Protein-Coupled Receptors 195
Gunnar Schulte

15 Dishevelled at the Crossroads of Pathways 207
Vítìzslav Bryja and Ondøej Bernatík

16 ?-Catenin: a Key Player in Both Cell Adhesion and Wnt Signaling 217
Jonathan Pettitt

17 Evolutionary Diversification of Vertebrate TCF/LEF Structure, Function, and Regulation 225
Stefan Hoppler and Marian L. Waterman

18 Insights from Structural Analysis of Protein–Protein Interactions by Wnt Pathway Components and Functional Multiprotein Complex Formation 239
Zhihong Cheng and Wenqing Xu

Part 3 Wnt Signaling in Embryonic Development and Adult Tissue Homeostasis 251

19 Wnt Signaling in Early Vertebrate Development: From Fertilization to Gastrulation 253
Eliza Zylkiewicz, Sergei Y. Sokol, and Stefan Hoppler

20 Wnt/?-Catenin Signaling in Embryonic Stem Cells: Insights into Early Mammalian Development 267
Kathryn C. Davidson

21 Wnt Signaling in Neural Development 279
Richard I. Dorsky

22 Wnt Signaling in Heart Organogenesis 293
Stefan Hoppler, Silvia Mazzotta, and Michael Kühl

23 Wnt Signaling in Kidney Organogenesis 303
Kimmo Halt and Seppo Vainio

24 Wnt Signaling Regulation of Tissue Architecture (EMT and MET) and Morphogenesis: Consequences for Colorectal and Liver Cancer 315
Theodora Fifis, Bang M. Tran, Renate H.M. Schwab, Timothy M. Johanson, Nadia Warner, Nick Barker, and Elizabeth Vincan

25 Wnt Signaling in Adult Stem Cells: Tissue Homeostasis and Regeneration 329
Frank J.T. Staal and Riccardo Fodde

26 Restoring Tissue Homeostasis: Wnt Signaling in Tissue Regeneration After Acute Injury 339
Günes Özhan and Gilbert Weidinger

Part 4 Wnt Signaling in Chronic Disease 357

27 Wnt Signaling and Colorectal Cancer 359
Kevin Myant and Owen J. Sansom

28 Wnt Signaling in Melanoma 369
Jamie N. Anastas and Andy J. Chien

29 Wnt Signaling in Mood and Psychotic Disorders 379
Stephen J. Haggarty, Karun Singh, Roy H. Perlis, and  Rakesh Karmacharya

30 Neuropsychiatric Disease-Associated Genetic Variation in the Wnt Pathway 393
Stephen J. Haggarty, Karun Singh, Roy H. Perlis, and Rakesh Karmacharya

31 Wnt Signaling in Dementia 411
Stephen J. Haggarty

32 Therapeutic Targeting of the Wnt Signaling Network 421
Felicity Rudge and Trevor Dale

Index 445

Customer Reviews

Biography

Stefan P. Hoppler, PhD, is Professor in Developmental Biology at the School of Medical Sciences at the University of Aberdeen. In addition to his teaching duties Prof. Hoppler runs research programs looking at Wnt inhibitors in heart muscle differentiation and tissue-specific regulation of gene expression by Wnt/beta-catenin signalling, and he also serves on the editorial board for the journal Developmental Dynamics.

Randall T. Moon, PhD, is Professor of Pharmacology at the University of Washington School of Medicine. His lab focuses on identifying the normal roles of Wnt signaling in embryos and adults and applying that knowledge to develop therapies for acute and chronic medical conditions involving Wnt signaling. Dr. Moon is Founding Director of the University of Washington Institute for Stem Cell and Regenerative Medicine, and a member of the Paul Allen Brain Institute Cell Networks Advisory Council, the HHMI Medical Research Fellows Program panel, and College of CSR Reviewers for NIH.