Zebrafish Nkd1 promotes Dvl degradation and is required for left–right patterning

Schneider, Igor; Schneider, P. J.; Derry, Sarah W.; Lin, Shengda; Barton, Lacy J.; Westfall, Trudi A.; Slusarski, Diane C.

doi:10.1016/j.ydbio.2010.08.040

Cited by 45 publications

(80 citation statements)

References 64 publications

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“…These data together indicate that -catenin signaling pathway is required for charon expression around the KV and this function is mainly mediated by ctnnb1 rather than ctnnb2. Recently, charon expression has been found to be transiently biased on the right side of KV in zebrafish embryos from 8-to 10-somite stages (Schneider et al, 2010). We found that knockdown of either ctnnb1 or ctnnb2 in DFCs did not significantly change the ratio of embryos with a right-side biased charon expression at the six-and 13-somite stages (data not shown).…”

Section: Research Articlementioning

confidence: 47%

“…In the past few years, studies in mouse and zebrafish have demonstrated that downregulation of several Wnt pathway components,e.g. zebrafish wnt3,wnt8,axin1,apc,gsk3b and nkd1 and mouse Wnt3a, disrupts normal LR development (Carl et al, 2007;Lin and Xu, 2009;Lee et al, 2007;Schneider et al, 2010;Nakaya et al, 2005). However, it is not clear whether and how endogenous -catenin affects LR asymmetry of vertebrate embryos.…”

Section: Endogenous -Catenin Is Required For Normal Laterality Develmentioning

confidence: 99%

“…It has been demonstrated that loss of function of many genes in DFCs, e.g. ntl (Amack and Yost, 2004;Amack et al, 2007), lrdr1 (dnah9 -Zebrafish Information Network) (Essner et al, 2005), axin1 (Schneider et al, 2008), nkd1 (Schneider et al, 2010), chordin and sox17 (Aamar and Dawid, 2010), leads to malformation of the KV and disruption of laterality.…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of constitutively active -catenin in medaka causes cardiac laterality defects . Dysregulation of Wnt signaling in zebrafish embryos has been found to cause LR defects (Carl et al, 2007;Caron et al, 2012;Lee et al, 2007;Lin and Xu, 2009;Schneider et al, 2010). The Wnt signaling pathway may regulate LR asymmetric development of vertebrate embryos by regulating ciliated organ formation and function (Schneider et al, 2010;Lin and Xu, 2009;Caron et al, 2012), the midline barrier formation (Danos and Yost, 1995;Lin and Xu, 2009;Nascone and Mercola, 1997) and bilateral Nodal signaling cascade (Rodriguez-Esteban et al, 2001;Carl et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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β-Catenin 1 and β-catenin 2 play similar and distinct roles in left-right asymmetric development of zebrafish embryos

Zhang

Lin

et al. 2012

Development

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SUMMARY-Catenin-mediated canonical Wnt signaling has been found to be required for left-right (LR) asymmetric development. However, the implication of endogenous -catenin in LR development has not been demonstrated by loss-of-function studies. In zebrafish embryos, two -catenin genes, -catenin 1 (ctnnb1) and -catenin 2 (ctnnb2) are maternally expressed and their zygotic expression occurs in almost all types of tissues, including Kupffer's vesicle (KV), an essential organ that initiates LR development in teleost fish. We demonstrate here that morpholino-mediated knockdown of ctnnb1, ctnnb2, or both, in the whole embryo or specifically in dorsal forerunner cells (DFCs) interrupts normal asymmetry of the heart, liver and pancreas. Global knockdown of ctnnb2 destroys the midline physical and molecular barrier, while global knockdown of ctnnb1 impairs the formation of the midline molecular barrier. Depletion of either gene or both in DFCs/KV leads to poor KV cell proliferation, abnormal cilia formation and disordered KV fluid flow with downregulation of ntl and tbx16 expression. ctnnb1 and ctnnb2 in DFCs/KV differentially regulate the expression of charon, a Nodal antagonist, and spaw, a key Nodal gene for laterality development in zebrafish. Loss of ctnnb1 in DFCs/KV inhibits the expression of charon around KV and of spaw in the posterior lateral plate mesoderm, while ctnnb2 knockdown results in loss of spaw expression in the anterior lateral plate mesoderm with little alteration of charon expression. Taken together, our findings suggest that ctnnb1 and ctnnb2 regulate multiple processes of laterality development in zebrafish embryos through similar and distinct mechanisms.

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Section: Research Articlementioning

confidence: 47%

Section: Endogenous -Catenin Is Required For Normal Laterality Develmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

β-Catenin 1 and β-catenin 2 play similar and distinct roles in left-right asymmetric development of zebrafish embryos

Zhang

Lin

et al. 2012

Development

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“…In Xenopus, Coco is the ortholog of Cerl2 and is the gene thought to respond earliest to leftward flow; it thus manifests asymmetric expression around the organizer and plays a role similar to that of Cerl2 (Schweickert et al, 2010), although histone deacetylase activity at earlier stages might be involved in epigenetic silencing of Nodal (Carneiro et al, 2011). In zebrafish and Medaka, Charon (Dand5 -Zebrafish Information Network), an ortholog of mouse Cerl2, is asymmetrically expressed (R>L) in KV and is indispensable for left and right asymmetry (Hashimoto et al, 2004;Schneider et al, 2010; Hojo et al, 2007;Lopes et al, 2010). Asymmetric signal generated in the node is transmitted to the surrounding tissues.…”

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confidence: 99%

Left-right patterning: conserved and divergent mechanisms

2012

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SummaryThe left-right (LR) asymmetry of visceral organs is fundamental to their function and position within the body. Over the past decade or so, the molecular mechanisms underlying the establishment of such LR asymmetry have been revealed in many vertebrate and invertebrate model organisms. These studies have identified a gene network that contributes to this process and is highly conserved from sea urchin to mouse. By contrast, some specific steps of the process, such as the symmetrybreaking event and situs-specific organogenesis, appear to have diverged during evolution. Here, we summarize the common and divergent mechanisms by which LR asymmetry is established in vertebrates. Key words: Nodal, Cilia, Left-right asymmetry IntroductionThe establishment of left-right (LR) asymmetry during early embryogenesis is crucial for the correct positioning and morphogenesis of internal organs. This process involves a number of intricately regulated developmental mechanisms, some of which appear to be conserved among vertebrates. For some organisms, LR symmetry breaking takes place around the left-right organizer (LR organizer; the node in mice, Hensen's node in the chick, the gastrocoel roof plate in Xenopus, and Kupffer's vesicle in zebrafish). In these animals, except for the chick and pig, asymmetric fluid flow produced by rotation of multiple cilia on the LR organizer results in asymmetric gene expression around the LR organizer. Earlier asymmetries in the localization of some molecules are observed in Xenopus and chick embryos and contribute to the establishment of LR asymmetry, but the roles of these molecules in establishing LR asymmetry in other organisms still need to be established (Spéder et al., 2007;Vandenberg and Levin, 2010). Following the symmetry-breaking event, asymmetric information is transmitted to surrounding tissues and induces the asymmetric expression of Nodal and Lefty. Nodal and Lefty, Development 139, 3257-3262 (2012) DEVELOPMENT 3258 members of the transforming growth factor  (TGF) superfamily, act as diffusible activator and inhibitor molecules, respectively, and constitute a self-enhancement and lateral-inhibition (SELI) system, which is highly conserved among vertebrates and some nonvertebrates, and provides robustness to LR determination. Finally, asymmetric Nodal signals induce the left-sided expression of other genes, such as pituitary homeobox 2 (Pitx2), which in turn contribute to the LR asymmetric morphogenesis of various visceral organs. The cellular mechanisms underlying situs-specific organogenesis, by contrast, seem to vary among vertebrates. Early asymmetriesIn Xenopus embryos, several genes exhibit asymmetric patterns of gene expression at early stages of development (Kramer et al., 2002; Fukumoto et al., 2005). The earliest LR asymmetry in Xenopus embryos described to date is the localization of H + -and K + -dependent ATPase mRNA and protein in the two-cell embryo (Aw et al., 2008); a few hours after fertilization, the amount of these mRNAs and protein is higher in one...

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Identification of colon tumor marker NKD1 via integrated bioinformatics analysis and experimental validation

Wang

Yang

et al. 2021

Cancer Medicine

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Background Colorectal cancer is an important death‐related disease in the worldwide. However, specific colon cancer tumor markers currently used for diagnosis and treatment are few. The purpose of this study is to screen the potential colon cancer markers by bioinformatics and verify the results with experiments. Methods Gene expression data were downloaded from two different databases: TCGA database and GEO datasets, which were then analyzed by two different methods (difference analysis and WGCNA method). Venn and PPI analysis obtained the potential core genes, which were then performed the GO enrichment and KEGG pathway analysis. Expressions levels of NKD1 in colon carcinoma tissues were further confirmed by immunohistochemical staining and western blot assays. Moreover, the function was measured by MTT, clone formation, and tumor transplantation experiments. Importantly, co‐immunoprecipitation, immunofluorescence, and protein stability assays were further performed to explore the underlying mechanism of NKD1 promoting cell proliferation. Results Nine potential core genes highly expressed in colon cancer samples were screened out by bioinformatics analysis. NKD1, one of the hub genes, highly expressed in the colon carcinoma tissues could enhance the proliferation of colon cancer cells. Mechanism research demonstrated that NKD1 was essential for the combination between Wnt signalosome (DVL) and β‐catenin, and that NKD1 knockout remarkably decreased the β‐catenin expression. Immunofluorescence assays further implied that NKD1 knockout significantly inhibited β‐catenin nuclear accumulation. Importantly, the stability of β‐catenin proteins was maintained by NKD1 in the colon cancer cells. Conclusion We believe that NKD1 well expressed in the colorectal carcinoma tissues can enhance the proliferation of colon cancer cells. Furthermore, the functions that NKD1 may have in colon cancer cells should be different from that NKD1 has played in the zebrafish. Thus, NKD1 could be a specific colorectal cancer marker.

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Zebrafish Nkd1 promotes Dvl degradation and is required for left–right patterning

Cited by 45 publications

References 64 publications

β-Catenin 1 and β-catenin 2 play similar and distinct roles in left-right asymmetric development of zebrafish embryos

β-Catenin 1 and β-catenin 2 play similar and distinct roles in left-right asymmetric development of zebrafish embryos

Left-right patterning: conserved and divergent mechanisms

Identification of colon tumor marker NKD1 via integrated bioinformatics analysis and experimental validation

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