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Invertebrates express a multitude of Wnt ligands and all Wnt/β-catenin signaling pathways converge to only one nuclear Lef/Tcf. In vertebrates, however, four distinct Lef/Tcfs, i.e. Tcf-1, Lef, Tcf-3, and Tcf-4 fulfill this function. At present, it is largely unknown to what extent the various Lef/Tcfs are functionally similar or diversified in vertebrates. In particular, it is not known which domains are responsible for the Tcf subtype specific functions. We investigated the conserved and non-conserved functions of the various Tcfs by using Xenopus laevis as a model organism and testing Tcfs from Hydra magnipapillata, Caenorhabditis elegans and Drosophila melanogaster. In order to identify domains relevant for the individual properties we created series of chimeric constructs consisting of parts of XTcf-3, XTcf-1 and HyTcf. Rescue experiments in Xenopus morphants revealed that the three invertebrate Tcfs tested compensated the loss of distinct Xenopus Tcfs: Drosophila Tcf (Pangolin) can substitute for the loss of XTcf-1, XTcf-3 and XTcf-4. By comparison, Caenorhabditis Tcf (Pop-1) and Hydra Tcf (HyTcf) can substitute for the loss of only XTcf-3 and XTcf-4, respectively. The domain, which is responsible for subtype specific functions is the regulatory CRD domain. A phylogenetic analysis separates Tcf-1/Lef-1 from the sister group Tcf-3/4 in the vertebrate lineage. We propose that the vertebrate specific diversification of Tcfs in vertebrates resulted in subfunctionalization of a Tcf that already united most of the Lef/Tcf functions. 相似文献
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Gangadhara Reddy Sareddy Sundaram Challa Manas Panigrahi Phanithi Prakash Babu 《Neurochemical research》2009,34(7):1278-1288
Although Wnt/β-catenin/Tcf signaling pathway has been shown to be a crucial factor in the development of many cancers, little
is known about its role in glioma malignancy. In the present study, we report the first evidence that Wnt/β-catenin/Tcf signaling
pathway is constitutively activated in experimental gliomas induced by single transplacental dose of N-ethyl-N-nitrosourea (ENU). In the present study we analyzed ENU induced rat gliomas of different stages (P90, P135 and P180) for the
expression of β-catenin, Lef1, Tcf4 and their targets c-Myc, N-Myc and cyclin D1. Western blot analysis revealed upregulation
of β-catenin, Lef1, Tcf4, c-Myc, N-Myc and cyclin D1 in gliomas compared to controls and their levels were progressively increased
from initial stage (P90) to progression stage (P180). In consistent with this, immunohistochemistry revealed the cytoplasmic
and nuclear accumulation of β-catenin, and nuclear positivity was evident for Lef1, Tcf4, c-Myc, N-Myc and cyclin D1. Based
on these results, we conclude that Wnt/β-catenin pathway may play a major role in the tumorigenesis and tumor progression
in ENU induced rat gliomas. 相似文献
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James M Wells Farzad Esni Gregory P Boivin Bruce J Aronow William Stuart Chelsea Combs Angela Sklenka Steven D Leach Andrew M Lowy 《BMC developmental biology》2007,7(1):4
Background
β-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of β-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that β-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of β-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of β-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of β-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed β-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis. 相似文献7.
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Background
The Wnt/Wg pathway plays an important role in the developmental program of many cells and tissues in a variety of organisms. In addition, many Wnts and components of their downstream signaling pathways, such as β-catenin and APC, have been implicated in tumorigenesis. Over the past years, several genes have been identified as Wnt responsive, including c-myc, siamois, and cyclin D1. 相似文献10.
Involvement of Tcf/Lef in establishing cell types along the animal-vegetal axis of sea urchins 总被引:1,自引:0,他引:1
Huang L Li X El-Hodiri HM Dayal S Wikramanayake AH Klein WH 《Development genes and evolution》2000,210(2):73-81
Members of the Tcf/Lef family interact with β-catenin to activate programs of gene expression during development. Recently
β-catenin was shown to be essential for establishing cell fate along the animal-vegetal axis of the sea urchin embryo. To
examine the role of Tcf/Lef in sea urchins we cloned a Strongylocentrotus purpuratus Tcf/Lef homolog. Expression of SpTcf/Lef was maximal when β-catenin became localized to nuclei of vegetal blastomeres, consistent with its acting in combination with
β-catenin to specify vegetal cell fates. Expression of a dominant-negative SpTcf/Lef inhibited primary and secondary mesenchyma, endoderm, and aboral ectoderm formation in a manner similar to that observed
when nuclear accumulation of β-catenin was prevented. Our results suggest that SpTcf/Lef functions by interacting with β-catenin
to specify cell fates along the sea urchin animal-vegetal axis.
Received: 6 July 1999 / Accepted: 27 August 1999 相似文献
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Raymond Poon Saeid Amini Nik Jessica Ahn Laura Slade Benjamin A Alman 《BMC cell biology》2009,10(1):38-10
Background
β-catenin and transforming growth factor β signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor β is partially mediated by β-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of β-catenin and its interaction with transforming growth factor β in cell motility and the induction of collagen lattice contraction. 相似文献13.
Sareddy GR Geeviman K Panigrahi M Challa S Mahadevan A Babu PP 《Neurochemical research》2012,37(1):96-104
Although pilocytic and diffuse grade II astrocytomas considered as low-grade tumors, the distinction between them is still
a major clinical problem. Previously we reported the activation of Wnt/β-catenin/Tcf signaling pathway in diffuse astrocytomas,
however its role in pilocytic astrocytomas is not well understood. In this study, we investigated the Wnt/β-catenin/Tcf pathway
in pilocytic astrocytomas and compared with diffuse astrocytomas. We observed the differential expression of β-catenin, Tcf4,
Lef1 and c-Myc in astrocytomas particularly higher levels were observed in pilocytic astrocytomas and GBM while very little
expression was documented in grade II tumors. Further, immunohistochemical analysis revealed the strong positivity of β-catenin,
Tcf4, Lef1 and c-Myc in pilocytic astrocytomas than that of grade II tumors and also exhibited the strong positivity in vascular
endothelial cells of pilocytic astrocytomas and GBM. Hence, Wnt/β-catenin/Tcf signaling pathway is differentially expressed
in astrocytomas, activation of this pathway might be helpful in separating pilocytic astrocytomas from low-grade diffuse astrocytomas. 相似文献
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Wnt genes encode secreted glycoproteins that act in cell–cell signalling to regulate a wide array of developmental processes,
ranging from cellular differentiation to axial patterning. Discovery that canonical Wnt/β-catenin signalling is responsible
for regulating head/tail specification in planarian regeneration has recently highlighted their importance in flatworm (phylum
Platyhelminthes) development, but examination of their roles in the complex development of the diverse parasitic groups has
yet to be conducted. Here, we characterise Wnt genes in the model tapeworm Hymenolepis microstoma and mine genomic resources of free-living and parasitic species for the presence of Wnts and downstream signalling components.
We identify orthologs through a combination of BLAST and phylogenetic analyses, showing that flatworms have a highly reduced
and dispersed complement that includes orthologs of only five subfamilies (Wnt1, Wnt2, Wnt4, Wnt5 and Wnt11) and fewer paralogs
in parasitic flatworms (5–6) than in planarians (9). All major signalling components are identified, including antagonists
and receptors, and key binding domains are intact, indicating that the canonical (Wnt/β-catenin) and non-canonical (planar
cell polarity and Wnt/Ca2+) pathways are functional. RNA-Seq data show expression of all Hymenolepis Wnts and most downstream components in adults and larvae with the notable exceptions of wnt1, expressed only in adults, and wnt2 expressed only in larvae. The distribution of Wnt subfamilies in animals corroborates the idea that the last common ancestor
of the Cnidaria and Bilateria possessed all contemporary Wnts and highlights the extent of gene loss in flatworms. 相似文献
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