XB-ART-50160
J Cell Sci
April 1, 2015;
128
(7):
1408-21.
Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling.
Fellgett SW
,
Maguire RJ
,
Pownall ME
.
Abstract
Wnt signalling plays essential roles during embryonic development and is known to be mis-regulated in human disease. There are many molecular mechanisms that ensure tight regulation of Wnt activity. One such regulator is the heparan-sulfate-specific 6-O-endosulfatase Sulf1. Sulf1 acts extracellularly to modify the structure of heparan sulfate chains to affect the bio-availability of Wnt ligands. Sulf1 could, therefore, influence the formation of Wnt signalling complexes to modulate the activation of both canonical and non-canonical pathways. In this study, we use well-established assays in Xenopus to investigate the ability of Sulf1 to modify canonical and non-canonical Wnt signalling. In addition, we model the ability of Sulf1 to influence morphogen gradients using fluorescently tagged Wnt ligands in ectodermal explants. We show that Sulf1 overexpression has ligand-specific effects on Wnt signalling: it affects membrane accumulation and extracellular levels of tagged Wnt8a and Wnt11b ligands differently, and inhibits the activity of canonical Wnt8a but enhances the activity of non-canonical Wnt11b.
PubMed ID: 25681501
PMC ID: PMC4379729
Article link: J Cell Sci
Grant support: [+]
Species referenced: Xenopus laevis
Genes referenced: atf2 chrd.1 ctnnb1 dvl2 fzd8 gnl3 lrp6 mmut myc nodal3.1 nodal3.2 odc1 ror2 sia1 sulf1 wnt11 wnt11b wnt3a wnt8a
Antibodies: HA Ab3 Myc Ab7
Article Images: [+] show captions
References [+] :
Ai,
QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling.
2003, Pubmed
Ai,
QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling.
2003,
Pubmed
Amaya, Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. 1991, Pubmed , Xenbase
Asashima, Mesodermal induction in early amphibian embryos by activin A (erythroid differentiation factor). 2020, Pubmed , Xenbase
Baeg, Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless. 2001, Pubmed
Cadigan, Wnt signaling: complexity at the surface. 2006, Pubmed
Christian, Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. 1991, Pubmed , Xenbase
Clevers, Wnt/beta-catenin signaling in development and disease. 2006, Pubmed
Cornell, Activin-mediated mesoderm induction requires FGF. 1994, Pubmed , Xenbase
Danesin, Ventral neural progenitors switch toward an oligodendroglial fate in response to increased Sonic hedgehog (Shh) activity: involvement of Sulfatase 1 in modulating Shh signaling in the ventral spinal cord. 2006, Pubmed
Dhoot, Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. 2001, Pubmed
Du, Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos. 1995, Pubmed , Xenbase
Esko, Order out of chaos: assembly of ligand binding sites in heparan sulfate. 2002, Pubmed
Faas, Overlapping functions of Cdx1, Cdx2, and Cdx4 in the development of the amphibian Xenopus tropicalis. 2009, Pubmed , Xenbase
Fisher, Cloning and characterisation of Myf5 and MyoD orthologues in Xenopus tropicalis. 2003, Pubmed , Xenbase
Fredieu, Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos. 1997, Pubmed , Xenbase
Freeman, Extracellular regulation of developmental cell signaling by XtSulf1. 2008, Pubmed , Xenbase
Gilchrist, Defining a large set of full-length clones from a Xenopus tropicalis EST project. 2004, Pubmed , Xenbase
Harland, In situ hybridization: an improved whole-mount method for Xenopus embryos. 1992, Pubmed , Xenbase
Hartley, Transgenic Xenopus embryos reveal that anterior neural development requires continued suppression of BMP signaling after gastrulation. 2002, Pubmed , Xenbase
He, LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. 2004, Pubmed
Heisenberg, Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. 2000, Pubmed
Hikasa, The Xenopus receptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signaling. 2002, Pubmed , Xenbase
Hitchins, Role of Sulf1A in Wnt1- and Wnt6-induced growth regulation and myoblast hyper-elongation. 2013, Pubmed
Häcker, Heparan sulphate proteoglycans: the sweet side of development. 2005, Pubmed
Isaacs, eFGF regulates Xbra expression during Xenopus gastrulation. 1994, Pubmed , Xenbase
Isaacs, Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification. 1992, Pubmed , Xenbase
Khurana, Role of heparan sulfatases in ovarian and breast cancer. 2013, Pubmed
Kikuchi, Selective activation mechanisms of Wnt signaling pathways. 2009, Pubmed
Kleinschmit, Drosophila heparan sulfate 6-O endosulfatase regulates Wingless morphogen gradient formation. 2010, Pubmed
Knights, De-regulated FGF receptors as therapeutic targets in cancer. 2010, Pubmed
Ku, Xwnt-11: a maternally expressed Xenopus wnt gene. 1994, Pubmed , Xenbase
Lamanna, Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling. 2008, Pubmed
Lemjabbar-Alaoui, Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. 2010, Pubmed
Leyns, Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. 1997, Pubmed , Xenbase
Li, HSulf-1 inhibits cell proliferation and invasion in human gastric cancer. 2012, Pubmed
Lin, Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. 1999, Pubmed
Logan, The Wnt signaling pathway in development and disease. 2004, Pubmed
MacDonald, Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6. 2004, Pubmed
MacMillan, Stage of breast cancer progression influences cellular response to activation of the WNT/planar cell polarity pathway. 2014, Pubmed
Mayor, The role of the non-canonical Wnt-planar cell polarity pathway in neural crest migration. 2013, Pubmed
McKendry, LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus nodal-related 3 promoter. 1998, Pubmed , Xenbase
Meyers, Sulf1 modulates BMP signaling and is required for somite morphogenesis and development of the horizontal myoseptum. 2013, Pubmed
Mikels, Wnts as ligands: processing, secretion and reception. 2006, Pubmed
Miller, Establishment of the dorsal-ventral axis in Xenopus embryos coincides with the dorsal enrichment of dishevelled that is dependent on cortical rotation. 1999, Pubmed , Xenbase
Molenaar, XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. 1996, Pubmed , Xenbase
Nawroth, Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. 2007, Pubmed
Nishita, Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells. 2010, Pubmed
Ohkawara, An ATF2-based luciferase reporter to monitor non-canonical Wnt signaling in Xenopus embryos. 2010, Pubmed , Xenbase
Piccolo, Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity. 1997, Pubmed , Xenbase
Pinson, An LDL-receptor-related protein mediates Wnt signalling in mice. 2000, Pubmed
Pownall, eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus. 1997, Pubmed , Xenbase
Ramsbottom, Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis. 2014, Pubmed , Xenbase
Rosen, Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate. 2010, Pubmed
Rothbächer, Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. 2000, Pubmed , Xenbase
Schambony, Wnt-5A/Ror2 regulate expression of XPAPC through an alternative noncanonical signaling pathway. 2007, Pubmed , Xenbase
Shi, FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. 2008, Pubmed , Xenbase
Smith, A mesoderm-inducing factor is produced by Xenopus cell line. 2004, Pubmed , Xenbase
Tada, Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. 2000, Pubmed , Xenbase
Tamai, LDL-receptor-related proteins in Wnt signal transduction. 2000, Pubmed , Xenbase
Tang, Functional consequences of the subdomain organization of the sulfs. 2009, Pubmed
Tao, Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. 2005, Pubmed , Xenbase
Touahri, Sulfatase 1 promotes the motor neuron-to-oligodendrocyte fate switch by activating Shh signaling in Olig2 progenitors of the embryonic ventral spinal cord. 2012, Pubmed
Tran, Heparan sulfate 6-O-endosulfatases (Sulfs) coordinate the Wnt signaling pathways to regulate myoblast fusion during skeletal muscle regeneration. 2012, Pubmed
Turnbull, Heparan sulfate: decoding a dynamic multifunctional cell regulator. 2001, Pubmed
Vivès, Post-Synthetic Regulation of HS Structure: The Yin and Yang of the Sulfs in Cancer. 2014, Pubmed
Wallingford, Dishevelled controls cell polarity during Xenopus gastrulation. 2000, Pubmed , Xenbase
Wallingford, Xenopus Dishevelled signaling regulates both neural and mesodermal convergent extension: parallel forces elongating the body axis. 2001, Pubmed , Xenbase
Wallingford, Convergent extension: the molecular control of polarized cell movement during embryonic development. 2002, Pubmed , Xenbase
Wang, Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. 1997, Pubmed , Xenbase
Wang, QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. 2004, Pubmed , Xenbase
Wehrli, arrow encodes an LDL-receptor-related protein essential for Wingless signalling. 2000, Pubmed
Wojcinski, DSulfatase-1 fine-tunes Hedgehog patterning activity through a novel regulatory feedback loop. 2011, Pubmed
Wolda, Overlapping expression of Xwnt-3A and Xwnt-1 in neural tissue of Xenopus laevis embryos. 1993, Pubmed , Xenbase
Yamamoto, Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. 2008, Pubmed
Yamamoto, Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. 2008, Pubmed , Xenbase
Yamanaka, Wnt11 stimulation induces polarized accumulation of Dishevelled at apical adherens junctions through Frizzled7. 2007, Pubmed , Xenbase
Yang-Snyder, A frizzled homolog functions in a vertebrate Wnt signaling pathway. 1997, Pubmed , Xenbase
Yost, The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. 1996, Pubmed , Xenbase
You, Sulfated is a negative feedback regulator of wingless in Drosophila. 2011, Pubmed
Amaya, Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. 1991, Pubmed , Xenbase
Asashima, Mesodermal induction in early amphibian embryos by activin A (erythroid differentiation factor). 2020, Pubmed , Xenbase
Baeg, Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless. 2001, Pubmed
Cadigan, Wnt signaling: complexity at the surface. 2006, Pubmed
Christian, Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. 1991, Pubmed , Xenbase
Clevers, Wnt/beta-catenin signaling in development and disease. 2006, Pubmed
Cornell, Activin-mediated mesoderm induction requires FGF. 1994, Pubmed , Xenbase
Danesin, Ventral neural progenitors switch toward an oligodendroglial fate in response to increased Sonic hedgehog (Shh) activity: involvement of Sulfatase 1 in modulating Shh signaling in the ventral spinal cord. 2006, Pubmed
Dhoot, Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. 2001, Pubmed
Du, Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos. 1995, Pubmed , Xenbase
Esko, Order out of chaos: assembly of ligand binding sites in heparan sulfate. 2002, Pubmed
Faas, Overlapping functions of Cdx1, Cdx2, and Cdx4 in the development of the amphibian Xenopus tropicalis. 2009, Pubmed , Xenbase
Fisher, Cloning and characterisation of Myf5 and MyoD orthologues in Xenopus tropicalis. 2003, Pubmed , Xenbase
Fredieu, Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos. 1997, Pubmed , Xenbase
Freeman, Extracellular regulation of developmental cell signaling by XtSulf1. 2008, Pubmed , Xenbase
Gilchrist, Defining a large set of full-length clones from a Xenopus tropicalis EST project. 2004, Pubmed , Xenbase
Harland, In situ hybridization: an improved whole-mount method for Xenopus embryos. 1992, Pubmed , Xenbase
Hartley, Transgenic Xenopus embryos reveal that anterior neural development requires continued suppression of BMP signaling after gastrulation. 2002, Pubmed , Xenbase
He, LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. 2004, Pubmed
Heisenberg, Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. 2000, Pubmed
Hikasa, The Xenopus receptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signaling. 2002, Pubmed , Xenbase
Hitchins, Role of Sulf1A in Wnt1- and Wnt6-induced growth regulation and myoblast hyper-elongation. 2013, Pubmed
Häcker, Heparan sulphate proteoglycans: the sweet side of development. 2005, Pubmed
Isaacs, eFGF regulates Xbra expression during Xenopus gastrulation. 1994, Pubmed , Xenbase
Isaacs, Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification. 1992, Pubmed , Xenbase
Khurana, Role of heparan sulfatases in ovarian and breast cancer. 2013, Pubmed
Kikuchi, Selective activation mechanisms of Wnt signaling pathways. 2009, Pubmed
Kleinschmit, Drosophila heparan sulfate 6-O endosulfatase regulates Wingless morphogen gradient formation. 2010, Pubmed
Knights, De-regulated FGF receptors as therapeutic targets in cancer. 2010, Pubmed
Ku, Xwnt-11: a maternally expressed Xenopus wnt gene. 1994, Pubmed , Xenbase
Lamanna, Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling. 2008, Pubmed
Lemjabbar-Alaoui, Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. 2010, Pubmed
Leyns, Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. 1997, Pubmed , Xenbase
Li, HSulf-1 inhibits cell proliferation and invasion in human gastric cancer. 2012, Pubmed
Lin, Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. 1999, Pubmed
Logan, The Wnt signaling pathway in development and disease. 2004, Pubmed
MacDonald, Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6. 2004, Pubmed
MacMillan, Stage of breast cancer progression influences cellular response to activation of the WNT/planar cell polarity pathway. 2014, Pubmed
Mayor, The role of the non-canonical Wnt-planar cell polarity pathway in neural crest migration. 2013, Pubmed
McKendry, LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus nodal-related 3 promoter. 1998, Pubmed , Xenbase
Meyers, Sulf1 modulates BMP signaling and is required for somite morphogenesis and development of the horizontal myoseptum. 2013, Pubmed
Mikels, Wnts as ligands: processing, secretion and reception. 2006, Pubmed
Miller, Establishment of the dorsal-ventral axis in Xenopus embryos coincides with the dorsal enrichment of dishevelled that is dependent on cortical rotation. 1999, Pubmed , Xenbase
Molenaar, XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. 1996, Pubmed , Xenbase
Nawroth, Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. 2007, Pubmed
Nishita, Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells. 2010, Pubmed
Ohkawara, An ATF2-based luciferase reporter to monitor non-canonical Wnt signaling in Xenopus embryos. 2010, Pubmed , Xenbase
Piccolo, Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity. 1997, Pubmed , Xenbase
Pinson, An LDL-receptor-related protein mediates Wnt signalling in mice. 2000, Pubmed
Pownall, eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus. 1997, Pubmed , Xenbase
Ramsbottom, Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis. 2014, Pubmed , Xenbase
Rosen, Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate. 2010, Pubmed
Rothbächer, Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. 2000, Pubmed , Xenbase
Schambony, Wnt-5A/Ror2 regulate expression of XPAPC through an alternative noncanonical signaling pathway. 2007, Pubmed , Xenbase
Shi, FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. 2008, Pubmed , Xenbase
Smith, A mesoderm-inducing factor is produced by Xenopus cell line. 2004, Pubmed , Xenbase
Tada, Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. 2000, Pubmed , Xenbase
Tamai, LDL-receptor-related proteins in Wnt signal transduction. 2000, Pubmed , Xenbase
Tang, Functional consequences of the subdomain organization of the sulfs. 2009, Pubmed
Tao, Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. 2005, Pubmed , Xenbase
Touahri, Sulfatase 1 promotes the motor neuron-to-oligodendrocyte fate switch by activating Shh signaling in Olig2 progenitors of the embryonic ventral spinal cord. 2012, Pubmed
Tran, Heparan sulfate 6-O-endosulfatases (Sulfs) coordinate the Wnt signaling pathways to regulate myoblast fusion during skeletal muscle regeneration. 2012, Pubmed
Turnbull, Heparan sulfate: decoding a dynamic multifunctional cell regulator. 2001, Pubmed
Vivès, Post-Synthetic Regulation of HS Structure: The Yin and Yang of the Sulfs in Cancer. 2014, Pubmed
Wallingford, Dishevelled controls cell polarity during Xenopus gastrulation. 2000, Pubmed , Xenbase
Wallingford, Xenopus Dishevelled signaling regulates both neural and mesodermal convergent extension: parallel forces elongating the body axis. 2001, Pubmed , Xenbase
Wallingford, Convergent extension: the molecular control of polarized cell movement during embryonic development. 2002, Pubmed , Xenbase
Wang, Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. 1997, Pubmed , Xenbase
Wang, QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. 2004, Pubmed , Xenbase
Wehrli, arrow encodes an LDL-receptor-related protein essential for Wingless signalling. 2000, Pubmed
Wojcinski, DSulfatase-1 fine-tunes Hedgehog patterning activity through a novel regulatory feedback loop. 2011, Pubmed
Wolda, Overlapping expression of Xwnt-3A and Xwnt-1 in neural tissue of Xenopus laevis embryos. 1993, Pubmed , Xenbase
Yamamoto, Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. 2008, Pubmed
Yamamoto, Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. 2008, Pubmed , Xenbase
Yamanaka, Wnt11 stimulation induces polarized accumulation of Dishevelled at apical adherens junctions through Frizzled7. 2007, Pubmed , Xenbase
Yang-Snyder, A frizzled homolog functions in a vertebrate Wnt signaling pathway. 1997, Pubmed , Xenbase
Yost, The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. 1996, Pubmed , Xenbase
You, Sulfated is a negative feedback regulator of wingless in Drosophila. 2011, Pubmed