Wnt Signaling

This book reflects the state of the art of our understanding of the WNT signaling system, which comprises a network of signaling pathways initiated by the secreted WNT lipoglycoproteins, which are crucial for embryonal development, stem cell regulation, tissue homeostasis and repair. Dysfunction of this evolutionarily conserved signaling system leads to many diseases including developmental disorders, diverse forms of cancer, fibrosis, neurodegenerative disease and many more. The WNT signaling system is built upon 19 mammalian, secreted WNT lipoglycoproteins that interact with a plethora of distinct receptors, such as the G protein-coupled receptors called Frizzleds (FZD1-10), LDL receptor-like proteins (LRP5/6), receptor tyrosine kinases (ROR1, 2, RYK and PTK7). In addition, WNT pathways are tightly regulated by many secreted and cell-intrinsic negative regulators, such as soluble FZD-related proteins (SFRPs), Dickkopfs (DKKs), WNT-inhibitory proteins, TIKI, RNF43 and more. Understanding the basic mechanism in terms of receptor-ligand interaction, receptor selectivity, signal initiation and desensitization remain poorly understood, even though substantial advances have been made the recent years. Due to the involvement of the WNT signaling system in human disease, it appears obvious to target diverse branches pharmacologically and therapeutically. However, given the complexity of the system and its importance for stem cell regulation and tissue maintenance, therapy comes with obvious risks for severe side effects. The field is addressing the challenge to identify suitable targets and selective compounds for therapy allowing disease-selective therapeutic effects and balancing unwanted side effects. This book summarizes the current understanding of the basic and applied pharmacology in the WNT signaling system and bridges disciplines such as pharmacology, physiology, neurosciences, oncology and drug development.

Wnt proteins are signaling molecules that play critical roles during embryonic development and in the regeneration of adult tissues. They bind to Frizzled and LRP family receptors on the cell surface, triggering a series of events that cause ?-catenin to enter the nucleus and activate transcription factors that control cell fate and cell proliferation. Mutations in components of the Wnt pathway lead to developmental defects and are common in cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of canonical Wnt signaling, as well as ?-catenin-independent Wnt signaling and cross-talk with other pathways. The contributors examine the numerous Wnt ligands; their production, secretion, and interactions with components of the extracellular environment; and details of the downstream signaling pathways that mediate the effects of Wnt proteins on cells. The roles of Wnt signaling in stem cell self-renewal, cell polarity, body-axis specification, wound healing, and other aspects of normal development and physiology are also covered. This volume includes discussion of Wnt signaling in cancer, skeletal defects, neurological disorders, and other human disease states. Thus, it is an indispensable reference for cell and developmental biologists as well as those, especially in the fields of stem cell biology and regenerative medicine, who are interested in targeting the Wnt pathway for therapeutic purposes.

Wnt signaling in Development and Disease: Molecular Mechanisms and Biological Functions reviews the core topics in Wnt signaling, from molecular pathway mechanisms to its role in embryogenesis, adult tissue homeostasis, and chronic disease. Written by a team of expert reviewers, the book provides clear and concise coverage of the core foundations of Wnt signaling before advancing to discussion of cutting-edge scientific research. Focused on the biological insights and current scientific questions of Wnt signaling, this book will be a comprehensive and definitive resource for a wide range of researchers and students in cell signaling, cell physiology, developmental biology, and biomedical engineering, as well as anyone interested in learning more about this important and complex protein network. • A definitive source of information on Wnt signaling and its role in development and disease, written by leaders in the field. • Explores the role of Wnt signaling in chronic disease such as melanoma, colorectal cancer, dementia, and psychiatric diseases • Reviews the complex processes of signal integration and regulation • Features broad discussion of Wnt signaling biology as well as detailed discussion of the pathway’s role in diseases and potential clinical applications.

The organizer area plays a central role in the formation of the embryonic axis and the central nervous system of all vertebrates including the human fetus. In The Vertebrate Organizer outstanding molecular development biologists and embryologists report their latest approaches in this fascinating research area using different vertebrate model organisms. The presented data are of central importance for the understanding of early human embryogenesis.

Wnt genes code for a family of secreted glycoproteins which fulfil important functions during the development of vertebrates and invertebrates. Wnts regulate as different aspects as differentiation, proliferation, cell migration, and cell polarity. Wnt proteins are able to activate different intracellular signaling cascades. This book describes different aspects of Wnt signaling during development of different species like the mouse, Xenopus, chicken, C. elegans or Drosophila and in different cellular contexts like heart formation or limb bud patterning. By doing such, this book provides, for the first time in printed form, an overview of the function of Wnt proteins during development. This book will be of interest to all professionals in the field of Wnt signaling, signal transduction or animal development.

The greatest mystery of life is how a single fertilized egg develops into a fully functioning, sometimes conscious multicellular organism. Embryogenesis Explained offers a new theory of how embryos build themselves, and combines simple physics with the most recent biochemical and genetic breakthroughs, based on the authors' prediction and then discovery of differentiation waves. They explain their ideas in a form accessible to the lay person and a broad spectrum of scientists and engineers. The diverse subjects of development, genetics and evolution, and their physics, are brought together to explain this major, previously unanswered scientific question of our time. As a follow up on The Hierarchical Genome, this book is a shorter but conceptually expanded work for the reader who is interested in science. It is useful as a starting point for the curious layman or the scientist or professional encountering the problem of embryogenesis without the formal biology background. There is also material useful for the seasoned biologist caught up in the new rush of information about the role of mechanics in developmental biology and cellular level mechanics in medicine.

WNT Signaling, Volume 153, the latest release in the Progress in Molecular Biology and Translational Science series, seeks to provide the most topical, informative, and exciting monographs available on a wide variety of research topics related to prions, viruses, bacteria and eukaryotes. The series provides readers with in-depth knowledge of important molecular biological aspects of organismal physiology and function, along with insights into how this knowledge may be applied to understand and ameliorate human disease. Each volume is edited by an internationally recognized expert who selects contributors at the forefront of a field. Accessible content that ideal for students and researchers alike Written by leading authorities in the field