XB-ART-55717
Dev Biol
January 1, 2019;
449
(1):
1-13.
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The Wnt inhibitor Dkk1 is required for maintaining the normal cardiac differentiation program in Xenopus laevis.
Guo Y
,
Dorn T
,
Kühl SJ
,
Linnemann A
,
Rothe M
,
Pfister AS
,
Vainio S
,
Laugwitz KL
,
Moretti A
,
Kühl M
.
Abstract
Wnt proteins can activate different intracellular signaling pathways. These pathways need to be tightly regulated for proper cardiogenesis. The canonical Wnt/β-catenin inhibitor Dkk1 has been shown to be sufficient to trigger cardiogenesis in gain-of-function experiments performed in multiple model systems. Loss-of-function studies however did not reveal any fundamental function for Dkk1 during cardiogenesis. Using Xenopus laevis as a model we here show for the first time that Dkk1 is required for proper differentiation of cardiomyocytes, whereas specification of cardiomyocytes remains unaffected in absence of Dkk1. This effect is at least in part mediated through regulation of non-canonical Wnt signaling via Wnt11. In line with these observations we also found that Isl1, a critical regulator for specification of the common cardiac progenitor cell (CPC) population, acts upstream of Dkk1.
PubMed ID: 30797757
PMC ID: PMC6496975
Article link: Dev Biol
Species referenced: Xenopus laevis
Genes referenced: alcam bmp4 ctnnb1 dkk1 frzb2 gata6 h3-3a hprt1 isl1 myh6 nkx2-5 tbx1 tbx5 tbxt tnni3 tnnt2 wnt11
GO keywords: Wnt signaling pathway [+]
Antibodies: Tnnt2 Ab1
Morpholinos: dkk1 MO1 isl1 MO1
Article Images: [+] show captions
References [+] :
Afouda,
Different requirements for GATA factors in cardiogenesis are mediated by non-canonical Wnt signaling.
2011, Pubmed,
Xenbase
Afouda,
Different requirements for GATA factors in cardiogenesis are mediated by non-canonical Wnt signaling.
2011,
Pubmed
,
Xenbase
Afouda, GATA transcription factors integrate Wnt signalling during heart development. 2009, Pubmed , Xenbase
Ai, Canonical Wnt signaling functions in second heart field to promote right ventricular growth. 2007, Pubmed
Behrens, Functional interaction of beta-catenin with the transcription factor LEF-1. 1996, Pubmed , Xenbase
Black, Transcriptional pathways in second heart field development. 2007, Pubmed
Bondue, Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. 2008, Pubmed
Brade, The amphibian second heart field: Xenopus islet-1 is required for cardiovascular development. 2008, Pubmed , Xenbase
Buckingham, Building the mammalian heart from two sources of myocardial cells. 2005, Pubmed
Cai, Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. 2004, Pubmed
Caneparo, Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek. 2007, Pubmed , Xenbase
Chen, Notch signaling respecifies the hemangioblast to a cardiac fate. 2008, Pubmed
Choudhry, DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation. 2013, Pubmed
David, MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling. 2008, Pubmed , Xenbase
Deroo, Global inhibition of Lef1/Tcf-dependent Wnt signaling at its nuclear end point abrogates development in transgenic Xenopus embryos. 2005, Pubmed , Xenbase
Dodou, Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. 2004, Pubmed
Dorn, Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity. 2016, Pubmed , Xenbase
Eisenberg, WNT11 promotes cardiac tissue formation of early mesoderm. 1999, Pubmed
Endo, Wnt-3a and Dickkopf-1 stimulate neurite outgrowth in Ewing tumor cells via a Frizzled3- and c-Jun N-terminal kinase-dependent mechanism. 2008, Pubmed
Garriock, Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus. 2005, Pubmed , Xenbase
Gessert, Comparative gene expression analysis and fate mapping studies suggest an early segregation of cardiogenic lineages in Xenopus laevis. 2009, Pubmed , Xenbase
Gessert, DM-GRASP/ALCAM/CD166 is required for cardiac morphogenesis and maintenance of cardiac identity in first heart field derived cells. 2008, Pubmed , Xenbase
Gessert, The multiple phases and faces of wnt signaling during cardiac differentiation and development. 2010, Pubmed
Gessert, Pescadillo is required for Xenopus laevis eye development and neural crest migration. 2007, Pubmed , Xenbase
Gibb, sfrp1 promotes cardiomyocyte differentiation in Xenopus via negative-feedback regulation of Wnt signalling. 2013, Pubmed , Xenbase
Glinka, Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. 1998, Pubmed , Xenbase
Gove, Over-expression of GATA-6 in Xenopus embryos blocks differentiation of heart precursors. 1997, Pubmed , Xenbase
Grieb, Predicting Variabilities in Cardiac Gene Expression with a Boolean Network Incorporating Uncertainty. 2016, Pubmed , Xenbase
Guo, Comparative analysis reveals distinct and overlapping functions of Mef2c and Mef2d during cardiogenesis in Xenopus laevis. 2014, Pubmed , Xenbase
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Hempel, A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects. 2019, Pubmed , Xenbase
Herrmann, A boolean model of the cardiac gene regulatory network determining first and second heart field identity. 2013, Pubmed
Huelsken, Requirement for beta-catenin in anterior-posterior axis formation in mice. 2000, Pubmed
Killick, Clusterin regulates β-amyloid toxicity via Dickkopf-1-driven induction of the wnt-PCP-JNK pathway. 2014, Pubmed
Krause, An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity. 2014, Pubmed
Krupnik, Functional and structural diversity of the human Dickkopf gene family. 1999, Pubmed , Xenbase
Kwon, Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. 2008, Pubmed
Laugwitz, Islet1 cardiovascular progenitors: a single source for heart lineages? 2008, Pubmed
Lavery, Wnt6 signaling regulates heart muscle development during organogenesis. 2008, Pubmed , Xenbase
Lian, Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. 2012, Pubmed
Lindsley, Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm. 2006, Pubmed
Lindsley, Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs. 2008, Pubmed
Liu, Requirement for Wnt3 in vertebrate axis formation. 1999, Pubmed
Mao, LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. 2001, Pubmed , Xenbase
Martin, Wnt/beta-catenin signalling regulates cardiomyogenesis via GATA transcription factors. 2010, Pubmed , Xenbase
Mazzotta, Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development. 2017, Pubmed
Monaghan, Dickkopf genes are co-ordinately expressed in mesodermal lineages. 2000, Pubmed , Xenbase
Moody, Segregation of fate during cleavage of frog (Xenopus laevis) blastomeres. 1991, Pubmed , Xenbase
Mukhopadhyay, Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. 2001, Pubmed , Xenbase
Nagy, Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and beta-catenin expression. 2010, Pubmed
Nakamura, Tissue- and stage-specific Wnt target gene expression is controlled subsequent to β-catenin recruitment to cis-regulatory modules. 2017, Pubmed , Xenbase
Onizuka, Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway. 2012, Pubmed
Pandur, Islet1-expressing cardiac progenitor cells: a comparison across species. 2013, Pubmed , Xenbase
Pandur, Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. 2002, Pubmed , Xenbase
Peterkin, GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation. 2003, Pubmed , Xenbase
Phillips, Dkk1 and Dkk2 regulate epicardial specification during mouse heart development. 2012, Pubmed
Rai, Continuous antagonism by Dkk1 counter activates canonical Wnt signaling and promotes cardiomyocyte differentiation of embryonic stem cells. 2012, Pubmed
Schneider, Wnt antagonism initiates cardiogenesis in Xenopus laevis. 2001, Pubmed , Xenbase
Semënov, Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. 2001, Pubmed , Xenbase
Session, Genome evolution in the allotetraploid frog Xenopus laevis. 2016, Pubmed , Xenbase
Terami, Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes. 2005, Pubmed , Xenbase
Ueno, Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. 2008, Pubmed
Wang, ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells. 2017, Pubmed
Willems, Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. 2011, Pubmed
Zhang, Wnt-mediated repression via bipartite DNA recognition by TCF in the Drosophila hematopoietic system. 2015, Pubmed
Zhou, Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2. 2008, Pubmed
Afouda, GATA transcription factors integrate Wnt signalling during heart development. 2009, Pubmed , Xenbase
Ai, Canonical Wnt signaling functions in second heart field to promote right ventricular growth. 2007, Pubmed
Behrens, Functional interaction of beta-catenin with the transcription factor LEF-1. 1996, Pubmed , Xenbase
Black, Transcriptional pathways in second heart field development. 2007, Pubmed
Bondue, Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. 2008, Pubmed
Brade, The amphibian second heart field: Xenopus islet-1 is required for cardiovascular development. 2008, Pubmed , Xenbase
Buckingham, Building the mammalian heart from two sources of myocardial cells. 2005, Pubmed
Cai, Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. 2004, Pubmed
Caneparo, Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek. 2007, Pubmed , Xenbase
Chen, Notch signaling respecifies the hemangioblast to a cardiac fate. 2008, Pubmed
Choudhry, DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart looping and differentiation. 2013, Pubmed
David, MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling. 2008, Pubmed , Xenbase
Deroo, Global inhibition of Lef1/Tcf-dependent Wnt signaling at its nuclear end point abrogates development in transgenic Xenopus embryos. 2005, Pubmed , Xenbase
Dodou, Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. 2004, Pubmed
Dorn, Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity. 2016, Pubmed , Xenbase
Eisenberg, WNT11 promotes cardiac tissue formation of early mesoderm. 1999, Pubmed
Endo, Wnt-3a and Dickkopf-1 stimulate neurite outgrowth in Ewing tumor cells via a Frizzled3- and c-Jun N-terminal kinase-dependent mechanism. 2008, Pubmed
Garriock, Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus. 2005, Pubmed , Xenbase
Gessert, Comparative gene expression analysis and fate mapping studies suggest an early segregation of cardiogenic lineages in Xenopus laevis. 2009, Pubmed , Xenbase
Gessert, DM-GRASP/ALCAM/CD166 is required for cardiac morphogenesis and maintenance of cardiac identity in first heart field derived cells. 2008, Pubmed , Xenbase
Gessert, The multiple phases and faces of wnt signaling during cardiac differentiation and development. 2010, Pubmed
Gessert, Pescadillo is required for Xenopus laevis eye development and neural crest migration. 2007, Pubmed , Xenbase
Gibb, sfrp1 promotes cardiomyocyte differentiation in Xenopus via negative-feedback regulation of Wnt signalling. 2013, Pubmed , Xenbase
Glinka, Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. 1998, Pubmed , Xenbase
Gove, Over-expression of GATA-6 in Xenopus embryos blocks differentiation of heart precursors. 1997, Pubmed , Xenbase
Grieb, Predicting Variabilities in Cardiac Gene Expression with a Boolean Network Incorporating Uncertainty. 2016, Pubmed , Xenbase
Guo, Comparative analysis reveals distinct and overlapping functions of Mef2c and Mef2d during cardiogenesis in Xenopus laevis. 2014, Pubmed , Xenbase
Hemmati-Brivanlou, Localization of specific mRNAs in Xenopus embryos by whole-mount in situ hybridization. 1992, Pubmed , Xenbase
Hempel, The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis. 2017, Pubmed , Xenbase
Hempel, A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects. 2019, Pubmed , Xenbase
Herrmann, A boolean model of the cardiac gene regulatory network determining first and second heart field identity. 2013, Pubmed
Huelsken, Requirement for beta-catenin in anterior-posterior axis formation in mice. 2000, Pubmed
Killick, Clusterin regulates β-amyloid toxicity via Dickkopf-1-driven induction of the wnt-PCP-JNK pathway. 2014, Pubmed
Krause, An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity. 2014, Pubmed
Krupnik, Functional and structural diversity of the human Dickkopf gene family. 1999, Pubmed , Xenbase
Kwon, Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. 2008, Pubmed
Laugwitz, Islet1 cardiovascular progenitors: a single source for heart lineages? 2008, Pubmed
Lavery, Wnt6 signaling regulates heart muscle development during organogenesis. 2008, Pubmed , Xenbase
Lian, Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. 2012, Pubmed
Lindsley, Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm. 2006, Pubmed
Lindsley, Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs. 2008, Pubmed
Liu, Requirement for Wnt3 in vertebrate axis formation. 1999, Pubmed
Mao, LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. 2001, Pubmed , Xenbase
Martin, Wnt/beta-catenin signalling regulates cardiomyogenesis via GATA transcription factors. 2010, Pubmed , Xenbase
Mazzotta, Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development. 2017, Pubmed
Monaghan, Dickkopf genes are co-ordinately expressed in mesodermal lineages. 2000, Pubmed , Xenbase
Moody, Segregation of fate during cleavage of frog (Xenopus laevis) blastomeres. 1991, Pubmed , Xenbase
Mukhopadhyay, Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. 2001, Pubmed , Xenbase
Nagy, Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and beta-catenin expression. 2010, Pubmed
Nakamura, Tissue- and stage-specific Wnt target gene expression is controlled subsequent to β-catenin recruitment to cis-regulatory modules. 2017, Pubmed , Xenbase
Onizuka, Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway. 2012, Pubmed
Pandur, Islet1-expressing cardiac progenitor cells: a comparison across species. 2013, Pubmed , Xenbase
Pandur, Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. 2002, Pubmed , Xenbase
Peterkin, GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation. 2003, Pubmed , Xenbase
Phillips, Dkk1 and Dkk2 regulate epicardial specification during mouse heart development. 2012, Pubmed
Rai, Continuous antagonism by Dkk1 counter activates canonical Wnt signaling and promotes cardiomyocyte differentiation of embryonic stem cells. 2012, Pubmed
Schneider, Wnt antagonism initiates cardiogenesis in Xenopus laevis. 2001, Pubmed , Xenbase
Semënov, Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. 2001, Pubmed , Xenbase
Session, Genome evolution in the allotetraploid frog Xenopus laevis. 2016, Pubmed , Xenbase
Terami, Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes. 2005, Pubmed , Xenbase
Ueno, Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. 2008, Pubmed
Wang, ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells. 2017, Pubmed
Willems, Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. 2011, Pubmed
Zhang, Wnt-mediated repression via bipartite DNA recognition by TCF in the Drosophila hematopoietic system. 2015, Pubmed
Zhou, Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2. 2008, Pubmed