Wnt Signaling In Development And Disease

Wnt Signaling in Stem Cells, Development and Regeneration, Volume 153, delves into the biology of Wnt signaling in a wide variety of model organisms. Since their first identification in 1982, Wnt proteins and their downstream effectors have captivated the attention of many researchers in a variety of fields, including developmental biology, cell signaling, structural biology, stem and cancer cell biology and regeneration. Wnt signaling, along with a small number of highly conserved signaling modules including the Hedgehog, FGF, BMP, RA and Notch pathways, orchestrates morphogenesis across all metazoans. Readers will find information on recent discoveries in the Wnt field, including interactions between Wnt and other signaling pathways, and tools and technologies to interrogate the complexity of Wnt signaling. Other chapters cover Wnt signaling in Xenopus neural development, Wnt signaling in hematopoietic stem cell development, Wnt signaling and the maintenance and regeneration of the gut epithelium, Wnt signaling in the skeleton as a basis for Wnt-based regenerative medicine, and Non-canonical Wnt5a-Ror signaling: Insights from human congenital disorders and cancer. Presents newest findings on the role of Wnt signaling in a variety of tissues and organisms Illustrates the diverse actions of Wnt signaling in development and disease Highlight tools and technologies to interrogate Wnt signaling in any biological system

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.

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.

Kidney Development and Disease brings together established and young investigators who are leading authorities in nephrology to describe recent advances in three primary areas of research. The first section describes the use of animal models as powerful tools for the discovery of numerous molecular mechanisms regulating kidney development. The second section focuses on nephric cell renewal and differentiation, which lead to diverse cell fates within the developing kidney, and discusses diseases resulting from the aberrant regulation of the balance between cell fate decisions. The final section concentrates on morphogenesis of the developing kidney and its maintenance after formation as well as the diseases resulting from failures in these processes. Kidney form and function have been extensively studied for centuries, leading to discoveries related to their development and disease. Recent scientific advances in molecular and imaging techniques have broadened our understanding of nephron development and maintenance as well as the diseases related to these processes.

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.

The formation of a complex multicellular organism from a single cell is one of the most amazing processes of biology. Embryonic development is characterised by the careful regulation of cellular behaviours such that cells proliferate, migrate, differentiate and form tissues at the correct place and time. These processes are genetically controlled and depend both on the history of cells, their lineage, and on the activities of signalling pathways, which coordinate the cell interactions leading to organogenesis. The aim of the Frontiers research topic “Signalling pathways in embryonic development” has been to provide a forum for experts in cell and developmental biology to share recent advances in the field of signalling during embryonic development. Sixteen articles in a variety of formats are united in this Topic, offering a valuable collection for researchers looking for an update in the knowledge of signalling pathways operating during embryogenesis. The works, focused mainly on vertebrates, explore different aspects of this theme from cell communication to organ formation and have implications for areas as distant as evolution or pathology. Understanding developmental signalling pathways is important for several reasons. It gives us information about basic mechanisms of cell function and interactions needed for morphogenesis and organogenesis. It uncovers the basis of congenital malformations, since errors at any step of cell signalling during development are a major cause of defects. This fundamental insight gives us clues to understand the mechanisms operating in evolution that explain diversity in form and function. And finally, it allows the identification of possible causes of disease in the adult organism (such as cancer or degenerative diseases) pinpointing possible targets for therapeutic approaches.

Inappropriate activation of the Wnt signaling pathway is observed in many human cancers and is sufficient to drive tumor initiation and progression in numerous contexts. Multiple mechanisms, such as overexpression of Wnt ligands, inactivation of the APC and Axin tumor suppressors, and mutation of -catenin, are responsible for pathway activation in tumor cells. The development of potent Wnt pathway antagonists for therapeutic use has been a major effort for investigators in both academia and industry in recent years. This book will provide an overview of the Wnt pathway as a therapeutic target for cancer, and discuss the preclinical development of inhibitors specifically directed to upstream and downstream components of the pathway.