The Experts below are selected from a list of 7665 Experts worldwide ranked by ideXlab platform
Jürgen Behrens - One of the best experts on this subject based on the ideXlab platform.
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Feedback Regulation of Mitochondrial Homeostasis via Wnt/β-catenin Signaling
Molecular & cellular oncology, 2018Co-Authors: Dominic B. Bernkopf, Jürgen BehrensAbstract:Cellular abundance of mitochondria is dynamically regulated. We could recently show that dysfunctional mitochondria release the phosphatase PGAM family member 5 (PGAM5) into the cytosol, where it interacts with the Wnt signaling-component AXIN1 and dephosphorylates AXIN1-bound β-catenin (CTNNB1) thereby activating Wnt/β-catenin signaling. Because Wnt/β-catenin signaling induces mitochondrial biogenesis dysfunctional mitochondria trigger their own replacement by releasing PGAM5.
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wnt β catenin signaling via axin2 is required for myogenesis and together with yap taz and tead1 active in iia iix muscle fibers
Development, 2016Co-Authors: Danyil Huraskin, Nane Eiber, Martin Reichel, Laura M Zidek, Bojana Kravic, Dominic B. Bernkopf, Jürgen Behrens, Julia Von Maltzahn, Said HashemolhosseiniAbstract:Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of AXIN1, increased together with Tead1 target gene expression. Furthermore, absence of AXIN1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.
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Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers.
Development, 2016Co-Authors: Danyil Huraskin, Nane Eiber, Martin Reichel, Laura M Zidek, Bojana Kravic, Dominic B. Bernkopf, Julia Von Maltzahn, Jürgen Behrens, Said HashemolhosseiniAbstract:Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of AXIN1, increased together with Tead1 target gene expression. Furthermore, absence of AXIN1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.
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Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention.
Journal of cell science, 2006Co-Authors: Eva Krieghoff, Jürgen Behrens, Bernhard MayrAbstract:beta-catenin is the central signalling molecule of the canonical Wnt pathway, where it activates target genes in a complex with LEF/TCF transcription factors in the nucleus. The regulation of beta-catenin activity is thought to occur mainly on the level of protein degradation, but it has been suggested that beta-catenin nuclear localization and hence its transcriptional activity may additionally be regulated via nuclear import by TCF4 and BCL9 and via nuclear export by APC and axin. Using live-cell microscopy and fluorescence recovery after photobleaching (FRAP), we have directly analysed the impact of these factors on the subcellular localization of beta-catenin, its nucleo-cytoplasmic shuttling and its mobility within the nucleus and the cytoplasm. We show that TCF4 and BCL9/Pygopus recruit beta-catenin to the nucleus, and APC, axin and axin2 enrich beta-catenin in the cytoplasm. Importantly, however, none of these factors accelerates the nucleo-cytoplasmic shuttling of beta-catenin, i.e. increases the rate of beta-catenin nuclear import or export. Moreover, the cytoplasmic enrichment of beta-catenin by APC and axin is not abolished by inhibition of CRM-1-dependent nuclear export. TCF4, APC, axin and axin2 move more slowly than beta-catenin in their respective compartment, and concomitantly decrease beta-catenin mobility. Together, these data indicate that beta-catenin interaction partners mainly regulate beta-catenin subcellular localization by retaining it in the compartment in which they are localized, rather than by active transport into or out of the nucleus.
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Deletions of AXIN1, a Component of the WNT/wingless Pathway, in Sporadic Medulloblastomas
Cancer research, 2001Co-Authors: R. P. Dahmen, Jürgen Behrens, Arend Koch, Dorota Denkhaus, Jörg-christian Tonn, Niels Sörensen, Frank Berthold, Walter Birchmeier, Otmar D. Wiestler, Torsten PietschAbstract:Medulloblastoma (MB) represents the most frequent malignant brain tumor in children. Most MBs appear sporadically; however, their incidence is highly elevated in two inherited tumor predisposition syndromes, Gorlin’s and Turcot’s syndrome. The genetic defects responsible for these diseases have been identified. Whereas Gorlin’s syndrome patients carry germ-line mutations in the patched ( PTCH ) gene, Turcot’s syndrome patients with MBs carry germ-line mutations of the adenomatous polyposis coli ( APC ) gene. The APC gene product is a component of a multiprotein complex controlling β-catenin degradation. In this complex, Axin plays a major role as scaffold protein. Whereas APC mutations are rare in sporadic MBs, a hot-spot region of β-catenin ( CTNNB1 ) mutations was identified in a subset of MBs. To find out if Axin is also involved in the pathogenesis of sporadic MBs, we analyzed 86 MBs and 11 MB cell lines for mutations in the AXIN1 gene. Using single-strand conformation polymorphism analysis, screening for large deletions by reverse transcription-PCR, and sequencing analysis, a single somatic point mutation in exon 1 (Pro255Ser) and seven large deletions (12%) of AXIN1 were detected. This indicates that AXIN1 may function as a tumor suppressor gene in MBs.
Frank Costantini - One of the best experts on this subject based on the ideXlab platform.
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wnt β catenin tcf signaling induces the transcription of axin2 a negative regulator of the signaling pathway
Molecular and Cellular Biology, 2002Co-Authors: Tong Zhang, Claire Domon, Jeannoel Freund, Frank CostantiniAbstract:Axin2/Conductin/Axil and its ortholog Axin are negative regulators of the Wnt signaling pathway, which promote the phosphorylation and degradation of beta-catenin. While Axin is expressed ubiquitously, Axin2 mRNA was seen in a restricted pattern during mouse embryogenesis and organogenesis. Because many sites of Axin2 expression overlapped with those of several Wnt genes, we tested whether Axin2 was induced by Wnt signaling. Endogenous Axin2 mRNA and protein expression could be rapidly induced by activation of the Wnt pathway, and Axin2 reporter constructs, containing a 5.6-kb DNA fragment including the promoter and first intron, were also induced. This genomic region contains eight Tcf/LEF consensus binding sites, five of which are located within longer, highly conserved noncoding sequences. The mutation or deletion of these Tcf/LEF sites greatly diminished induction by beta-catenin, and mutation of the Tcf/LEF site T2 abolished protein binding in an electrophoretic mobility shift assay. These results strongly suggest that Axin2 is a direct target of the Wnt pathway, mediated through Tcf/LEF factors. The 5.6-kb genomic sequence was sufficient to direct the tissue-specific expression of d2EGFP in transgenic embryos, consistent with a role for the Tcf/LEF sites and surrounding conserved sequences in the in vivo expression pattern of Axin2. Our results suggest that Axin2 participates in a negative feedback loop, which could serve to limit the duration or intensity of a Wnt-initiated signal.
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wnt β catenin tcf signaling induces the transcription of axin2 a negative regulator of the signaling pathway
Molecular and Cellular Biology, 2002Co-Authors: Eekhoon Jho, Tong Zhang, Claire Domon, Jeannoel Freund, Chounki Joo, Frank CostantiniAbstract:Axin2/Conductin/Axil and its ortholog Axin are negative regulators of the Wnt signaling pathway, which promote the phosphorylation and degradation of beta-catenin. While Axin is expressed ubiquitously, Axin2 mRNA was seen in a restricted pattern during mouse embryogenesis and organogenesis. Because many sites of Axin2 expression overlapped with those of several Wnt genes, we tested whether Axin2 was induced by Wnt signaling. Endogenous Axin2 mRNA and protein expression could be rapidly induced by activation of the Wnt pathway, and Axin2 reporter constructs, containing a 5.6-kb DNA fragment including the promoter and first intron, were also induced. This genomic region contains eight Tcf/LEF consensus binding sites, five of which are located within longer, highly conserved noncoding sequences. The mutation or deletion of these Tcf/LEF sites greatly diminished induction by beta-catenin, and mutation of the Tcf/LEF site T2 abolished protein binding in an electrophoretic mobility shift assay. These results strongly suggest that Axin2 is a direct target of the Wnt pathway, mediated through Tcf/LEF factors. The 5.6-kb genomic sequence was sufficient to direct the tissue-specific expression of d2EGFP in transgenic embryos, consistent with a role for the Tcf/LEF sites and surrounding conserved sequences in the in vivo expression pattern of Axin2. Our results suggest that Axin2 participates in a negative feedback loop, which could serve to limit the duration or intensity of a Wnt-initiated signal.
Hans Clevers - One of the best experts on this subject based on the ideXlab platform.
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wnt signaling through inhibition of β catenin degradation in an intact AXIN1 complex
Cell, 2012Co-Authors: Vivian S W Li, Wouter R. Karthaus, Jan P. Gerlach, Shabaz Mohammed, Albert J. R. Heck, Madelon M. Maurice, Tokameh Mahmoudi, Ser Sue Ng, Paul J Boersema, Hans CleversAbstract:Degradation of cytosolic β-catenin by the APC/AXIN1 destruction complex represents the key regulated step of the Wnt pathway. It is incompletely understood how the AXIN1 complex exerts its Wnt-regulated function. Here, we examine the mechanism of Wnt signaling under endogenous levels of the AXIN1 complex. Our results demonstrate that β-catenin is not only phosphorylated inside the AXIN1 complex, but also ubiquinated and degraded via the proteasome, all within an intact AXIN1 complex. In disagreement with current views, we find neither a disassembly of the complex nor an inhibition of phosphorylation of AXIN1-bound β-catenin upon Wnt signaling. Similar observations are made in primary intestinal epithelium and in colorectal cancer cell lines carrying activating Wnt pathway mutations. Wnt signaling suppresses β-catenin ubiquitination normally occurring within the complex, leading to complex saturation by accumulated phospho-β-catenin. Subsequently, newly synthesized β-catenin can accumulate in a free cytosolic form and engage nuclear TCF transcription factors.
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Abstract 983: Wnt pathway activation involves inhibition of β-catenin ubiquitination within the endogenous AXIN1 complex
Molecular and Cellular Biology, 2012Co-Authors: Wouter R. Karthaus, Jan P. Gerlach, Shabaz Mohammed, Albert J. R. Heck, Madelon M. Maurice, Tokameh Mahmoudi, Hans CleversAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Degradation of cytosolic β-catenin by the APC/AXIN1 Destruction Complex represents the key regulated step of the Wnt pathway. It is incompletely understood how the AXIN1 complex exerts its Wnt-regulated function. We have now examined the compositional change of the endogenous AXIN1 complex in HEK293T cells upon Wnt signaling. Our results demonstrate that not only phosphorylation, but also ubiquitination and proteasomal degradation of β-catenin occur within the AXIN1 complex. In disagreement with current views, we find neither a disassembly of the complex, nor an inhibition of phosphorylation of AXIN1-bound β-catenin upon Wnt signaling. Comparable observations are made in primary intestinal epithelium and in colorectal cancer cell lines carrying activating Wnt pathway mutations. Wnt signaling induces the loss of the dedicated E3 ligase α-TrCP from the complex, leading to complex saturation by accumulated phospho-β-catenin. Subsequently, newly synthesized β-catenin can accumulate in a free cytosolic form, travel to the nucleus and engage the TCF Wnt effector transcription factors. In contrast to current belief, the Axin complex remains compositionally intact in APC-mutant colorectal cancer. Rather, failure of β-catenin ubiquitination is the principle biochemical activating event in these malignant cells. Together we demonstrate a novel mechanism of the destruction complex for Wnt signal activation in both physiological and malignant states. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 983. doi:1538-7445.AM2012-983
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MAP3K1 functionally interacts with AXIN1 in the canonical Wnt signalling pathway
Biological chemistry, 2010Co-Authors: Tokameh Mahmoudi, Shabaz Mohammed, Albert J. R. Heck, Paul J Boersema, Pantelis Hatzis, Hans CleversAbstract:A central point of regulation in the Wnt/beta-catenin signalling pathway is the formation of the beta-catenin destruction complex. AXIN1, an essential negative regulator of Wnt signalling, serves as a scaffold within this complex and is critical for rapid turnover of beta-catenin. To examine the mechanism by which Wnt signalling disables the destruction complex, we used an immunoprecipitation-coupled proteomics approach to identify novel endogenous binding partners of AXIN1. We found mitogen-activated protein kinase kinase kinase 1 (MAP3K1) as an AXIN1 interactor in Ls174T colorectal cancer (CRC) cells. Importantly, confirmation of this interaction in HEK293T cells indicated that the AXIN1-MAP3K1 interaction is induced and modulated by Wnt stimulation. siRNA depletion of MAP3K1 specifically abrogated TCF/LEF-driven transcription and Wnt3A-driven endogenous gene expression in both HEK293T as well as DLD-1 CRC. Expression of ubiquitin ligase mutants of MAP3K1 abrogated TCF/LEF transcription, whereas kinase mutants had no effect in TCF-driven activity, highlighting the essential role of the MAP3K1 E3 ubiquitin ligase activity in regulation of the Wnt/beta-catenin pathway. These results suggest that MAP3K1, previously reported as an AXIN1 inter-actor in c-Jun NH(2)-terminal kinase pathway, is also involved in the canonical Wnt signalling pathway and positively regulates expression of Wnt target genes.
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Ectopic Wnt signal determines the eyeless phenotype of zebrafish masterblind mutant.
Development (Cambridge England), 2001Co-Authors: S Van De Water, M Van De Wetering, Hans Clevers, Jos Joore, J Esseling, Robert J. Bink, Danica ZivkovicAbstract:masterblind ( mbl ) is a zebrafish mutation characterised by the absence or reduction in size of the telencephalon, optic vesicles and olfactory placodes. We show that inhibition of Gsk3β in zebrafish embryos either by overexpression of dominant negative dn gsk3β mRNA or by lithium treatment after the midblastula transition phenocopies mbl . The loss of anterior neural tissue in mbl and lithium-treated embryos is preceded by posteriorization of presumptive anterior neuroectoderm during gastrulation, which is evident from the anterior shift of marker genes Otx2 and Wnt1 . Heterozygous mbl embryos showed increased sensitivity to inhibition of GSK3β by lithium or dn Xgsk3β that led to the loss of eyes. Overexpression of gsk3β mRNA rescued eyes and the wild-type fgf8 expression of homozygous mbl embryos. emx1 that delineates the telencephalon is expanded and shifted ventroanteriorly in mbl embryos. In contrast to fgf8 , the emx1 expression domain was not restored upon overexpression of gsk3β mRNA. These experiments place mbl as an antagonist of the Wnt pathway in parallel or upstream of the complex consisting of Axin, APC and Gsk3β that binds and phosphorylates β-catenin, thereby destabilising it. mbl maps on LG 3 close to a candidate gene AXIN1 . In mbl we detected a point mutation in the conserved minimal Gsk3β-binding domain of AXIN1 leading to a leucine to glutamine substitution at position 399. Overexpression of wild-type AXIN1 mRNA rescued mbl completely, demonstrating that mutant AXIN1 is responsible for the mutant phenotype. Overexpression of mutant L399Q AXIN1 in wild-type embryos resulted in a dose-dependent dominant negative activity as demonstrated by the loss of telencephalon and eyes. We suggest that the function of AXIN1/Mbl protein is to antagonise the Wnt signal and in doing so to establish and maintain the most anterior CNS. Our findings provide new insights into the mechanisms by which the Wnt pathway generates anteroposterior polarity of the neural plate.
Yongjiu Zhang - One of the best experts on this subject based on the ideXlab platform.
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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/β-catenin pathway via AXIN1 deubiquitination.
Cell biology international, 2020Co-Authors: Tong Huang, Qingquan Zhang, Wei Ren, Bing Yan, Tielun Tang, Hai Lin, Yongjiu ZhangAbstract:Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/β-catenin pathway. We found that USP44 overexpression increased the AXIN1 protein while decreasing β-catenin, c-myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/β-catenin pathway. Moreover, we found that two Wnt/β-catenin activators, LiCl and SKL2001, both attenuated oeUSP44-mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/β-catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the AXIN1 mRNA level. Further study uncovered that USP44 interacted with AXIN1 and reduced the ubiquitination of AXIN1. Furthermore, AXIN1 knock-down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/β-catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/β-catenin pathway via AXIN1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy.
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usp44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the wnt β catenin pathway via AXIN1 deubiquitination
Cell Biology International, 2020Co-Authors: Tong Huang, Qingquan Zhang, Wei Ren, Bing Yan, Tielun Tang, Hai Lin, Yongjiu ZhangAbstract:Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/β-catenin pathway. We found that USP44 overexpression increased the AXIN1 protein while decreasing β-catenin, c-myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/β-catenin pathway. Moreover, we found that two Wnt/β-catenin activators, LiCl and SKL2001, both attenuated oeUSP44-mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/β-catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the AXIN1 mRNA level. Further study uncovered that USP44 interacted with AXIN1 and reduced the ubiquitination of AXIN1. Furthermore, AXIN1 knock-down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/β-catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/β-catenin pathway via AXIN1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy.
Said Hashemolhosseini - One of the best experts on this subject based on the ideXlab platform.
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wnt β catenin signaling via axin2 is required for myogenesis and together with yap taz and tead1 active in iia iix muscle fibers
Development, 2016Co-Authors: Danyil Huraskin, Nane Eiber, Martin Reichel, Laura M Zidek, Bojana Kravic, Dominic B. Bernkopf, Jürgen Behrens, Julia Von Maltzahn, Said HashemolhosseiniAbstract:Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of AXIN1, increased together with Tead1 target gene expression. Furthermore, absence of AXIN1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.
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Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers.
Development, 2016Co-Authors: Danyil Huraskin, Nane Eiber, Martin Reichel, Laura M Zidek, Bojana Kravic, Dominic B. Bernkopf, Julia Von Maltzahn, Jürgen Behrens, Said HashemolhosseiniAbstract:Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of AXIN1, increased together with Tead1 target gene expression. Furthermore, absence of AXIN1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.