Wnt Function
Published by Anonymous on 2007/9/30 (2706 reads)
1: Oncogene. 2006 Dec 4;25(57):7469-81.
Function and biological roles of the Dickkopf family of Wnt modulators.
Niehrs C.
Department of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany. Niehrs@DKFZ-Heidelberg.DE
Dickkopf (Dkk) genes comprise an evolutionary conserved small gene family of four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy). They encode secreted proteins that typically antagonize Wnt/beta-catenin signaling, by inhibiting the Wnt coreceptors Lrp5 and 6. Additionally, Dkks are high affinity ligands for the transmembrane proteins Kremen1 and 2, which also modulate Wnt signaling. Dkks play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer's disease.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 17143291 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: DNA Cell Biol. 2005 Jul;24(7):446-57.
Wnt influence on chondrocyte differentiation and cartilage function.
Yates KE, Shortkroff S, Reish RG.
Department of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. kyates@partners.org
The Wnt signaling network regulates chondrocyte differentiation, proliferation, and maturation during embryonic limb development. In this review, we summarize studies of Wnt signaling during the chondrocyte life cycle in avian and mammalian systems, both before and after birth. Recent reports that implicate abnormal Wnt signaling as a contributing factor to pathogenic joint conditions are also discussed. In addition, we show new data that suggests Wnt signaling is active in adult cartilage. Overall, it appears that the Wnt network has dual roles in cartilage, as has been described in other tissues: it is an important regulator of chondrocyte development, but deregulated signaling is detrimental to mature tissues and may lead to disease.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 16008513 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: Curr Opin Cell Biol. 2004 Dec;16(6):681-7.
Wnt signaling and the regulation of stem cell function.
Kléber M, Sommer L.
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, CH-8093 Zurich, Switzerland. maurice.kleber@cell.biol.ethz.ch
Canonical Wnt signaling plays a crucial role in controlling cell expansion in many types of stem cells. Recent studies, however, demonstrated that Wnt is not only a general stem cell growth factor but can also influence cell lineage decisions in certain stem cell types by promoting specific fates at the expense of others. Thus, Wnt signaling elicits multiple functions in stem cells. Wnt activity appears to depend on cell-intrinsic properties that might change with time during development, thereby altering the cellular response to Wnt. Moreover, the spatial context of a stem cell also determines how the cell interprets Wnt signal activity, in that synergistic or antagonistic signaling pathways can modulate Wnt signaling. How a stem cell integrates Wnt and other signals and how such signaling networks regulate stem cell function on the molecular level remains to be elucidated.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15530781 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Brain Res Brain Res Rev. 2000 Aug;33(1):1-12.
Wnt signaling function in Alzheimer's disease.
De Ferrari GV, Inestrosa NC.
Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Alzheimer's disease (AD) is a neurodegenerative disease with progressive dementia accompanied by three main structural changes in the brain: diffuse loss of neurons; intracellular protein deposits termed neurofibrillary tangles (NFT) and extracellular protein deposits termed amyloid or senile plaques, surrounded by dystrophic neurites. Two major hypotheses have been proposed in order to explain the molecular hallmarks of the disease: The 'amyloid cascade' hypothesis and the 'neuronal cytoskeletal degeneration' hypothesis. While the former is supported by genetic studies of the early-onset familial forms of AD (FAD), the latter revolves around the observation in vivo that cytoskeletal changes - including the abnormal phosphorylation state of the microtubule associated protein tau - may precede the deposition of senile plaques. Recent studies have suggested that the trafficking process of membrane associated proteins is modulated by the FAD-linked presenilin (PS) proteins, and that amyloid beta-peptide deposition may be initiated intracellularly, through the secretory pathway. Current hypotheses concerning presenilin function are based upon its cellular localization and its putative interaction as macromolecular complexes with the cell-adhesion/signaling beta-catenin molecule and the glycogen synthase kinase 3beta (GSK-3beta) enzyme. Developmental studies have shown that PS proteins function as components in the Notch signal transduction cascade and that beta-catenin and GSK-3beta are transducers of the Wnt signaling pathway. Both pathways are thought to have an important role in brain development, and they have been connected through Dishevelled (Dvl) protein, a known transducer of the Wnt pathway. In addition to a review of the current state of research on the subject, we present a cell signaling model in which a sustained loss of function of Wnt signaling components would trigger a series of misrecognition events, determining the onset and development of AD.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10967351 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Oncogene. 1999 Dec 20;18(55):7860-72.
Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways.
Miller JR, Hocking AM, Brown JD, Moon RT.
Department of Pharmacology and Center for Developmental Biology, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Communication between cells is often mediated by secreted signaling molecules that bind cell surface receptors and modulate the activity of specific intracellular effectors. The Wnt family of secreted glycoproteins is one group of signaling molecules that has been shown to control a variety of developmental processes including cell fate specification, cell proliferation, cell polarity and cell migration. In addition, mis-regulation of Wnt signaling can cause developmental defects and is implicated in the genesis of several human cancers. The importance of Wnt signaling in development and in clinical pathologies is underscored by the large number of primary research papers examining various aspects of Wnt signaling that have been published in the past several years. In this review, we will present a synopsis of current research with particular attention paid to molecular mechanism of Wnt signal transduction and how the mis-regulation of Wnt signaling leads to cancer.
Publication Types:
Review
PMID: 10630639 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Bioessays. 1994 Jun;16(6):395-404.
Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling.
Siegfried E, Perrimon N.
Department of Genetics, Harvard Medical School, Boston, MA 02115.
The link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int-1) was identified over a decade ago as a proto-oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int-1 supported the notion that int-1 may have a role in normal development. In the last few years it has been recognized that int-1 and Wingless belong to a large family of related glyco-proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 8080429 [PubMed - indexed for MEDLINE]
Function and biological roles of the Dickkopf family of Wnt modulators.
Niehrs C.
Department of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany. Niehrs@DKFZ-Heidelberg.DE
Dickkopf (Dkk) genes comprise an evolutionary conserved small gene family of four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy). They encode secreted proteins that typically antagonize Wnt/beta-catenin signaling, by inhibiting the Wnt coreceptors Lrp5 and 6. Additionally, Dkks are high affinity ligands for the transmembrane proteins Kremen1 and 2, which also modulate Wnt signaling. Dkks play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer's disease.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 17143291 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: DNA Cell Biol. 2005 Jul;24(7):446-57.
Wnt influence on chondrocyte differentiation and cartilage function.
Yates KE, Shortkroff S, Reish RG.
Department of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. kyates@partners.org
The Wnt signaling network regulates chondrocyte differentiation, proliferation, and maturation during embryonic limb development. In this review, we summarize studies of Wnt signaling during the chondrocyte life cycle in avian and mammalian systems, both before and after birth. Recent reports that implicate abnormal Wnt signaling as a contributing factor to pathogenic joint conditions are also discussed. In addition, we show new data that suggests Wnt signaling is active in adult cartilage. Overall, it appears that the Wnt network has dual roles in cartilage, as has been described in other tissues: it is an important regulator of chondrocyte development, but deregulated signaling is detrimental to mature tissues and may lead to disease.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 16008513 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: Curr Opin Cell Biol. 2004 Dec;16(6):681-7.
Wnt signaling and the regulation of stem cell function.
Kléber M, Sommer L.
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, CH-8093 Zurich, Switzerland. maurice.kleber@cell.biol.ethz.ch
Canonical Wnt signaling plays a crucial role in controlling cell expansion in many types of stem cells. Recent studies, however, demonstrated that Wnt is not only a general stem cell growth factor but can also influence cell lineage decisions in certain stem cell types by promoting specific fates at the expense of others. Thus, Wnt signaling elicits multiple functions in stem cells. Wnt activity appears to depend on cell-intrinsic properties that might change with time during development, thereby altering the cellular response to Wnt. Moreover, the spatial context of a stem cell also determines how the cell interprets Wnt signal activity, in that synergistic or antagonistic signaling pathways can modulate Wnt signaling. How a stem cell integrates Wnt and other signals and how such signaling networks regulate stem cell function on the molecular level remains to be elucidated.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15530781 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Brain Res Brain Res Rev. 2000 Aug;33(1):1-12.
Wnt signaling function in Alzheimer's disease.
De Ferrari GV, Inestrosa NC.
Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Alzheimer's disease (AD) is a neurodegenerative disease with progressive dementia accompanied by three main structural changes in the brain: diffuse loss of neurons; intracellular protein deposits termed neurofibrillary tangles (NFT) and extracellular protein deposits termed amyloid or senile plaques, surrounded by dystrophic neurites. Two major hypotheses have been proposed in order to explain the molecular hallmarks of the disease: The 'amyloid cascade' hypothesis and the 'neuronal cytoskeletal degeneration' hypothesis. While the former is supported by genetic studies of the early-onset familial forms of AD (FAD), the latter revolves around the observation in vivo that cytoskeletal changes - including the abnormal phosphorylation state of the microtubule associated protein tau - may precede the deposition of senile plaques. Recent studies have suggested that the trafficking process of membrane associated proteins is modulated by the FAD-linked presenilin (PS) proteins, and that amyloid beta-peptide deposition may be initiated intracellularly, through the secretory pathway. Current hypotheses concerning presenilin function are based upon its cellular localization and its putative interaction as macromolecular complexes with the cell-adhesion/signaling beta-catenin molecule and the glycogen synthase kinase 3beta (GSK-3beta) enzyme. Developmental studies have shown that PS proteins function as components in the Notch signal transduction cascade and that beta-catenin and GSK-3beta are transducers of the Wnt signaling pathway. Both pathways are thought to have an important role in brain development, and they have been connected through Dishevelled (Dvl) protein, a known transducer of the Wnt pathway. In addition to a review of the current state of research on the subject, we present a cell signaling model in which a sustained loss of function of Wnt signaling components would trigger a series of misrecognition events, determining the onset and development of AD.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10967351 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Oncogene. 1999 Dec 20;18(55):7860-72.
Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways.
Miller JR, Hocking AM, Brown JD, Moon RT.
Department of Pharmacology and Center for Developmental Biology, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Communication between cells is often mediated by secreted signaling molecules that bind cell surface receptors and modulate the activity of specific intracellular effectors. The Wnt family of secreted glycoproteins is one group of signaling molecules that has been shown to control a variety of developmental processes including cell fate specification, cell proliferation, cell polarity and cell migration. In addition, mis-regulation of Wnt signaling can cause developmental defects and is implicated in the genesis of several human cancers. The importance of Wnt signaling in development and in clinical pathologies is underscored by the large number of primary research papers examining various aspects of Wnt signaling that have been published in the past several years. In this review, we will present a synopsis of current research with particular attention paid to molecular mechanism of Wnt signal transduction and how the mis-regulation of Wnt signaling leads to cancer.
Publication Types:
Review
PMID: 10630639 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Bioessays. 1994 Jun;16(6):395-404.
Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling.
Siegfried E, Perrimon N.
Department of Genetics, Harvard Medical School, Boston, MA 02115.
The link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int-1) was identified over a decade ago as a proto-oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int-1 supported the notion that int-1 may have a role in normal development. In the last few years it has been recognized that int-1 and Wingless belong to a large family of related glyco-proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 8080429 [PubMed - indexed for MEDLINE]
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