A Transgenic Lef1/β-Catenin-Dependent Reporter Is Expressed in Spatially Restricted Domains throughout Zebrafish Development
Open accessAbstract
The Wnt/beta-catenin signaling pathway plays multiple roles during embryonic development, only a few of which have been extensively characterized. Although domains of Wnt expression have been identified throughout embryogenesis, anatomical and molecular characterization of responding cells has been mostly unexplored. We have generated a transgenic zebrafish line that expresses a destabilized green fluorescent protein (GFP) variant under the control of a beta-catenin responsive promoter. Early zygotic expression of this transgene (TOPdGFP) mirrors known domains of Wnt signaling in the embryo. Loss of Lef1 activity results in decreased reporter expression and posterior defects, while loss of Tcf3 (Headless, Hdl) activity does not alter reporter expression, even though it results in loss of forebrain structures. In addition, ectopic Wnt1 expression can activate the reporter. In older embryos, we identify a number of transgene-expressing cell populations as novel sites of beta-catenin signaling. We conclude that our TOP-dGFP reporter line faithfully illustrates domains of beta-catenin activity and enables the identification of responsive cell populations.
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HB-EGF increased gfp mRNA in Müller glia of TOP:dGFP Wnt reporter fish.
“Consistent with the idea that HB-EGF mediates the effects of retinal injury on the Wnt signaling pathway, we found that HB-EGF stimulated β-catenin nuclear accumulation in MG derived progenitors (Figure 7A) and gfp mRNA expression in MG of the Wnt signaling reporter fish TOP:dGFP (Figure 7B) (Dorsky et al., 2002).”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Dorsky et al., 2002
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“The role of the Wnt pathway in cell fate determination was demonstrated for neural crest cells (Brault et al., 2001; Dorsky et al., 2002) and for hematopoietic cells, for which a role in proliferation and stem cell self-renewal was also reported (Austin et al., 1997; Brandon et al., 2000; Reya et…”
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“Despite this latent b-catenin reduction, we did not detect any changes in b-catenin activity as measured by a cotransfected Wnt/b-catenin-responsive reporter, TOP-dGFP (Dorsky et al., 2002), or find any correlation between reporter expression and the endogenous pattern of Foxp4 expression (Figures S2S–S2V).”
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“Although this is consistent with chick and zebrafish transgenic Wnt pathway reporters (Cho and Cepko, 2006; Dorsky et al., 2002), particular mouse TCF/LEF reporters show differences in activity in the developing RPE (this study) (Fuhrmann et al., 2009; Liu et al., 2006).”
BackgroundWehner, D., Tsarouchas, T. M., Michael, A., Haase, C., Weidinger, G., Reimer, M. M., Becker, T., & Becker, C. G. (2017) · Nature Communications · doi:10.1038/s41467-017-00143-0 · Cited by 175 · see citing works
Lush, M. E., Diaz, D. C., Koenecke, N., Baek, S., Boldt, H., Peter, M. S., Gaitán-Escudero, T., Romero‐Carvajal, A., Busch‐Nentwich, E. M., Perera, A. G., et al. (2019) · eLife · doi:10.7554/elife.44431 · Cited by 160 · see citing works
“…(Rohs et al., 2013), dld (Jiang et al., 2014), wnt2 (Poulain and Ober, 2011), wnt10a (Lush and Piotrowski, 2014b), wnt11r (Duncan et al., 2015), gfp (Dorsky et al., 2002), atoh1a and notch3 (Itoh and Chitnis, 2001) and sfrp1a (Tendeng and Houart, 2006) Additional probes were generated by PCR from…”
MethodWnt signaling in eye organogenesis
Fuhrmann, S. (2008) · Organogenesis · doi:10.4161/org.4.2.5850 · Cited by 165 · see citing works
Zhang, J., Woodhead, G. J., Swaminathan, S. K., Noles, S. R., McQuinn, E. R., Pisarek-Horowitz, A., Stocker, A. M., Mutch, C. A., Funatsu, N., & Chenn, A. (2010) · Developmental Cell · doi:10.1016/j.devcel.2009.12.025 · Cited by 168 · see citing works
“(E) Dual TOPdGFP/mCherry reporter (Figs.”
BackgroundInfluentialRetinal stem cells and regeneration
Moshiri, A., Close, J., & Reh, T. A. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041870am · Cited by 166 · see citing works
“Transgenic zebrafish with a reporter construct for Wnt pathway activation (Lef1) show a high level of activity in the ciliary epithelium and iris (Dorsky et al., 2002).”
BackgroundIntegration of Telencephalic Wnt and Hedgehog Signaling Center Activities by Foxg1
Danesin, C., Peres, J., Johansson, M., Snowden, V., Cording, A., Papalopulu, N., & Houart, C. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.03.007 · Cited by 164 · see citing works
North, T. E., Babu, I. R., Vedder, L. M., Lord, A. M., Wishnok, J. S., Tannenbaum, S. R., Zon, L. I., & Goessling, W. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008209107 · Cited by 158 · see citing works
“To document hepatic wnt activation in zebrafish, Tg(TOP:GFP)w25 wnt reporter embryos (referred to as TOP:GFP) (26) were exposed to APAP at 48 hpf; markedly increased fluorescence was found in livers of treated fish at 72 hpf (Fig.”
BackgroundMethodInfluentialTransgenic Wnt/TCF pathway reporters: all you need is Lef?
Barolo, S. (2006) · Oncogene · doi:10.1038/sj.onc.1210057 · Cited by 157 · see citing works
“A multimerized TCF site reporter created for zebrafish, called TOPdGFP, was also derived from TOPFLASH, but uses a destabilized form of GFP as a reporter gene (Dorsky et al., 2002).”
BackgroundMethodInfluentialBellipanni, G., Varga, M., Maegawa, S., Imai, Y., Kelly, C., Myers, A. P., Chu, F., Talbot, W. S., & Weinberg, E. S. (2006) · Development · doi:10.1242/dev.02295 · Cited by 148 · see citing works
“Ventralizing and posteriorizing Wnt signals also appear to be dependent on -catenin (Dorsky et al., 2002; Weidinger et al., 2005) and thus, may be impaired in embryos with -catenin deficiencies.”
BackgroundAlexander, M. S., Kawahara, G., Motohashi, N., Casar, J. C., Eisenberg, I., Myers, J. A., Gasperini, M. J., Estrella, E. A., Kho, A. T., Mitsuhashi, S., et al. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.62 · Cited by 146 · see citing works
Twotcf3genes cooperate to pattern the zebrafish brain
Dorsky, R. I., Itoh, M., Moon, R. T., & Chitnis, A. B. (2003) · Development · doi:10.1242/dev.00402 · Cited by 146 · see citing works
“At shield stage the ventrolateral blastoderm margin in zebrafish is the source of caudalizing factors and corresponds with the highest β-catenin activity (Woo and Fraser, 1997; Dorsky et al., 2002).”
Self-citationFujimura, N., Taketo, M. M., Mori, M., Kořínek, V., & Kozmík, Z. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.07.002 · Cited by 145 · see citing works
“In addition, active Wnt/ β-catenin signaling is detected in the presumptive RPE not only in mice but also in chickens, fishes, and frogs (Dorsky et al., 2002; Cho and Cepko, 2006; Kreslova et al., 2007; Liu et al., 2006; Van Raay et al., 2005; Veien et al., 2008).”
BackgroundHow do they do Wnt they do?: regulation of transcription by the Wnt/β‐catenin pathway
Archbold, H. C., Yang, Y., Chen, L., & Cadigan, K. M. (2011) · Acta Physiologica · doi:10.1111/j.1748-1716.2011.02293.x · Cited by 141 · see citing works
“…(Korinek et al. 1997, Lum et al. 86 2011 The Authors Acta Physiologica 2011 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2011.02293.x 2003, DasGupta et al. 2005) and in transgenic mice and fish (DasGupta & Fuchs 1999, Dorsky et al. 2002, Maretto et al. 2003, Nakaya et al. 2005).”
BackgroundInfluentialStem Cells and Calcium Signaling
Tonelli, F. P., Santos, A., Gomes, D. A., da Silva, S. L., Gomes, K. N., Ladeira, L., & Resende, R. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-94-007-2888-2_40 · Cited by 142 · see citing works
“reported the development of a technique for long-term imaging of regulated gene expression in zebrafish [120].”
MethodYokota, Y., Kim, W.-Y., Chen, Y., Wang, X., Stanco, A., Komuro, Y., Snider, W. D., & Anton, E. S. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.053 · Cited by 134 · see citing works
“To examine if the nuclear localized β-catenin is transcriptionally active in APC deficient cortex, we electroporated a reporter construct that expresses a destabilized GFP variant under the control of a β-catenin responsive promoter (TOPdGFP; Dorsky et al., 2002).”
Sequential and Opposing Activities of Wnt and BMP Coordinate Zebrafish Bone Regeneration
Stewart, S., Gomez, A. W., Armstrong, B. E., Henner, A. L., & Stankunas, K. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.010 · Cited by 126 · see citing works
“control of a synthetic Wnt-responsive promoter (Dorsky et al., 2002).”
Maher, M. T., Flozak, A. S., Stocker, A. M., Chenn, A., & Gottardi, C. J. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200811108 · Cited by 123 · see citing works
“Indeed, an MDCK clone that stably expresses a TCF optimal promoter (TOP)–destabilized GFP (dGFP; Dorsky et al., 2002) shows enhanced reporter activation in cells along the colony edge (Fig.”
BackgroundInfluentialBuilding the posterior lateral line system in zebrafish
Chitnis, A. B., Nogare, D. D., & Matsuda, M. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20962 · Cited by 122 · see citing works
“Fluorescent reporter lines also exist for visualizing the pattern of Notch (Yeo et al., 2007; Parsons et al., 2009), FGF (Molina et al., 2007), and Lef/Tcf signaling (Dorsky et al., 2002; Valdivia et al., 2011).”
BackgroundShimizu, N., Kawakami, K., & Ishitani, T. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.07.016 · Cited by 121 · see citing works
Peukert, D., Weber, S., Lumsden, A., & Scholpp, S. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001218 · Cited by 118 · see citing works
Agathocleous, M., Iordanova, I., Willardsen, M. I., Xue, X. Y., Vetter, M. L., Harris, W. A., & Moore, K. B. (2009) · Development · doi:10.1242/dev.040451 · Cited by 114 · see citing works
“Sox2BD(–), which lacks the DNA-binding domain but retains the C-terminus, had a similar activity to Sox2 itself in suppressing TOP-dGFP expression (Fig.”
InfluentialRepression of the vertebrate organizer by Wnt8 is mediated by Vent and Vox
Ramel, M., & Lekven, A. C. (2004) · Development · doi:10.1242/dev.01277 · Cited by 116 · see citing works
“First, we examined the expression of the Wnt/βcatenin activity reporter TOPdGFP (Dorsky et al., 2002; Lewis et al., 2004).”
InfluentialBeta-catenin signaling in prostate cancer: an early perspective.
Chesire, D. R., & Isaacs, W. B. (2003) · Endocrine Related Cancer · doi:10.1677/erc.0.0100537 · Cited by 115 · see citing works
“…modus operandi are staining studies examining the expression of known CRT targets (Batlle et al. 2002, Leung et al. 2002), as well as transgenic models that allow one to assess CRT on a global level through monitoring expression of a proxy target gene (DasGupta & Fuchs 1999, Dorsky et al. 2002).”
BackgroundZhang, J., Shemezis, J. R., McQuinn, E. R., Wang, J., Sverdlov, M., & Chenn, A. (2013) · Neural Development · doi:10.1186/1749-8104-8-7 · Cited by 107 · see citing works
“To examine the cell-autonomous role of N-cadherin in β-catenin signaling in VZ precursors, we co-electroporated expression plasmids for Cre recombinase and TOPdGFP [23] into the VZ of E13.”
MethodSensory hair cell regeneration in the zebrafish lateral line
Lush, M. E., & Piotrowski, T. (2014) · Developmental Dynamics · doi:10.1002/dvdy.24167 · Cited by 112 · see citing works
“Finally, the generation of fluorescent transgenic lines enables the in vivo visualization and tracking of specific cell types or sub-cellular compartments or serve as reporters for different signaling pathways, such as Wnt/b-catenin and Notch (Dorsky et al., 2002; Parsons et al., 2009; Shimizu et al., 2012; Moro et al…”
BackgroundCanonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis
Lee, J. E., Wu, S., Goering, L. M., & Dorsky, R. I. (2006) · Development · doi:10.1242/dev.02613 · Cited by 112 · see citing works
“To address this issue, we performed immunohistochemistry for GFP protein after injecting wnt8b or lef1 MOs into TOPdGFP embryos.”
InfluentialSelf-citationGonad Differentiation in Zebrafish Is Regulated by the Canonical Wnt Signaling Pathway1
Sreenivasan, R., Jiang, J., Wang, X., Bártfai, R., Kwan, H. Y., Christoffels, A. G., & Orbán, L. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.110874 · Cited by 105 · see citing works
Kamm, G. B., Pisciottano, F., Kliger, R., & Franchini, L. F. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst023 · Cited by 102 · see citing works
“To generate transgenic zebrafish, we subcloned each of the 14 HAEs in an Tol2-based expression vector upstream of a mouse c-fos minimal promoter (Dorsky et al. 2002) followed by EGFP coding sequences (Kawakami et al. 2004; Fisher, Grice, Vinton, Bessling, Urasaki, et al. 2006).”
BackgroundMethodMapping Canonical Wnt Signaling in the Developing and Adult Retina
Liu, H., Thurig, S., Mohamed, O. A., Dufort, D., & Wallace, V. A. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0403 · Cited by 105 · see citing works
“Activation of a Lef1/ -catenin– dependent reporter gene in transgenic fish was also described in the retinal pigmented epithelium (RPE), CM, and lens.(42) From the (1)Molecular Medicine Program, Ottawa Health Research Institute, and University of Ottawa Eye Institute, Ottawa, Ontario, Canada; the (2)Center for Neuromu…”
BackgroundMasai, I., Yamaguchi, M., Tonou‐Fujimori, N., Komori, A., & Okamoto, H. (2005) · Development · doi:10.1242/dev.01714 · Cited by 105 · see citing works
“To elucidate whether Wnt signalling is activated by PKA, Development 132 (7) Research article D ev el op m en t 1545Hh-PKA pathway regulates RGC differentiation we used TOPdGFP transgenic fish carrying GFP under the control of a β-catenin responsive promoter (Dorsky et al., 2002).”
MethodInfluentialTransgenic fluorescent zebrafish lines that have revolutionized biomedical research
Choe, C. P., Choi, S., Kee, Y., Kim, J. M., Kim, S.-H., Lee, Y., Park, H., & Ro, H. (2021) · Laboratory Animal Research · doi:10.1186/s42826-021-00103-2 · Cited by 96 · see citing works
“In the Tg(top:GFP) transgenic line, the fluorescent reporter is under the control of TOPFlash comprising four consensus TCF/LEF binding elements juxtaposed to a c-fos minimal promoter [17, 18].”
BackgroundTemporally coordinated signals progressively pattern the anteroposterior and dorsoventral body axes
Tuazon, F. B., & Mullins, M. C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.06.003 · Cited by 98 · see citing works
Thorpe, C. J., Weidinger, G., & Moon, R. T. (2005) · Development · doi:10.1242/dev.01733 · Cited by 96 · see citing works
“One possible explanation to account for our observations is that Wnts could be acting as anti-differentiation factors in the presomitic mesoderm, where Wnt activity is localized, as determined by expression of the TOPdGFP reporter (Dorsky et al., 2002) (C.T., unpublished).”
BackgroundMethodInfluentialSelf-citationWnt1 and wnt10b function redundantly at the zebrafish midbrain–hindbrain boundary
Lekven, A. C., Buckles, G. R., Kostakis, N., & Moon, R. T. (2003) · Developmental Biology · doi:10.1016/s0012-1606(02)00044-1 · Cited by 95 · see citing works
Self-citationFOXP1 potentiates Wnt/β-catenin signaling in diffuse large B cell lymphoma
Walker, M. P., Stopford, C. M., Cederlund, M. L., Fang, F., Jahn, C., Rabinowitz, A. D., Goldfarb, D., Graham, D. M., Yan, F., Deal, A. M., et al. (2015) · Science Signaling · doi:10.1126/scisignal.2005654 · Cited by 94 · see citing works
“A digoxigenin-labeled antisense RNA probe was prepared from a template encoding d2EGFP (corresponding to residues 422 to 461 of mouse ornithine decarboxylase) (80).”
MethodVisualization of estrogen receptor transcriptional activation in zebrafish.
Gorelick, D. A., & Halpern, M. (2011) · Endocrinology · doi:10.1210/en.2010-1257 · Cited by 95 · see citing works
Regulation of Slug transcription in embryonic ectoderm by β‐catenin‐Lef/Tcf and BMP‐Smad signaling
Sakai, D., Tanaka, Y., Endo, Y., Osumi, N., Okamoto, H., & Wakamatsu, Y. (2005) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2005.00821.x · Cited by 94 · see citing works
“TOP-flash, which contains six repeats of the Lef/Tcf binding sites and has been widely used to detect canonical Wnt signal (van de Wetering et al. 1997; Roose et al. 1998; DasGupta & Fuchs 1999; Merrill et al. 2001; Drosky et al. 2002; Marret et al. 2003), responded to the coexpression of Lef1 and CA-β-catenin in the…”
MethodWIKI4, a Novel Inhibitor of Tankyrase and Wnt/ß-Catenin Signaling
James, R. G., Davidson, K. C., Bosch, K. A., Biechele, T. L., Robin, N. C., Taylor, R. J., Major, M. B., Camp, N. D., Fowler, K., Martins, T. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050457 · Cited by 93 · see citing works
Self-citationNuclear signaling from cadherin adhesion complexes
McCrea, P. D., Maher, M. T., & Gottardi, C. J. (2015) · Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2014.11.018 · Cited by 85 · see citing works
Jacques, B. E., Montgomery, W. H., Uribe, P. M., Yatteau, A. T., Asuncion, J. D., Resendiz, G., Matsui, J. I., & Dabdoub, A. (2013) · Developmental Neurobiology · doi:10.1002/dneu.22134 · Cited by 89 · see citing works
“The other construct, TOP-ndsRed, derived from the TOPFLASH construct (Dorsky et al., 2002), is a single reporter in which nuclear red fluorescence indicates cells with active Wnt/b-catenin signaling.”
BackgroundNrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability
Ishitani, T., Matsumoto, K., Chitnis, A. B., & Itoh, M. (2005) · Nature Cell Biology · doi:10.1038/ncb1311 · Cited by 89 · see citing works
“TOPdGFP fish embryos express green fluorescent protein (GFP) in the neural-crest region as previously publishe”
Riley, B. B., Chiang, M., Storch, E. M., Heck, R., Buckles, G. R., & Lekven, A. C. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20133 · Cited by 88 · see citing works
“…address boundary-specific functions, we used an alternative approach to specifically ablate rhombomere boundaries: wild-type embryos were injected with morpholino oligomers (MOs) to knockdown tcf3b, one of several mediators of Wnt signaling in the head (Kim et al., 2000; Dorsky et al., 2002, 2003).”
MethodWnt Signaling Regulates Postembryonic Hypothalamic Progenitor Differentiation
Wang, X., Kopinke, D., Lin, J., McPherson, A. D., Duncan, R. N., Otsuna, H., Moro, E., Hoshijima, K., Grunwald, D. J., Argenton, F., et al. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.07.012 · Cited by 87 · see citing works
“We used both TOP:GFP, a Wnt reporter containing 4 TCF binding sites upstream of a destabilized GFP transgene (Dorsky et al., 2002) as well as TCFSiam:GFP, a Wnt reporter containing the Xenopus siamois promoter upstream of eGFP (Moro et al.”
MethodSelf-citationMahmoudi, T., Boj, S. F., Hatzis, P., Li, V. S. W., Taouatas, N., Vries, R. G. J., Teunissen, H., Begthel, H., Korving, J., Mohammed, S., et al. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000539 · Cited by 86 · see citing works
Thomas-Jinu, S., Gordon, P. M., Fielding, T., Taylor, R., Smith, B. N., Snowden, V., Blanc, E., Vance, C. A., Topp, S. D., Wong, C. H., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.026 · Cited by 86 · see citing works
“…ID: ZDB-TGCONSTRCT-070117-161 Zebrafish: Tg(1.4dlx5a-dlx6a:gfp)ot1 Ghanem et al., 2003 ZFIN ID: ZDB-TGCONSTRCT-070117-17 Zebrafish: Tg(TOP:gfp)w25 Dorsky et al., 2002 ZFIN ID: ZDB-TGCONSTRCT-070117-137 Zebrafish: Tg(Bactin:HRAS-EGFP)vu119 Cooper et al., 2005 ZFIN ID:…”
Hübner, K., Cabochette, P., Diéguez‐Hurtado, R., Wiesner, C., Wakayama, Y., Grassme, K. S., Hubert, M., Günther, S., Belting, H., Affolter, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07302-x · Cited by 85 · see citing works
Ancient Vertebrate Conserved Noncoding Elements Have Been Evolving Rapidly in Teleost Fishes
Lee, A., Kerk, S. Y., Tan, Y., Brenner, S., & Venkatesh, B. (2010) · Molecular Biology and Evolution · doi:10.1093/molbev/msq304 · Cited by 85 · see citing works
Wnt Signaling Regulates Multipolar-to-Bipolar Transition of Migrating Neurons in the Cerebral Cortex
Boitard, M., Bocchi, R., Egervari, K., Petrenko, V., Viale, B., Gremaud, S., Zgraggen, E., Salmon, P., & Kiss, J. Z. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.061 · Cited by 83 · see citing works
“We took advantage of a Wnt canonical signaling-dependent reporter construct (M38 TOPdGFP) that expresses a destabilized GFP (dGFP) variant under the control of four b-catenin-responsive TCF/ LEF-1 consensus sequences (Li et al., 1998; Dorsky et al., 2002; Hurlstone et al., 2003; Munji et al., 2011; Woodhead et al., 20…”
BackgroundWnt signaling and neural stem cells: caught in the Wnt web
Michaelidis, T. M., & Lie, D. C. (2007) · Cell and Tissue Research · doi:10.1007/s00441-007-0476-5 · Cited by 80 · see citing works
“For example, in Xenopus, LEF-1 functions as a Wnt-dependent activator, whereas the Tcf members act both as repressors and activators (Dorsky et al. 2002; Gradl et al. 2002; Houston et al. 2002; Standley et al. 2006).”
BackgroundMutch, C. A., Schulte, J. D., Olson, E. C., & Chenn, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012376 · Cited by 79 · see citing works
A direct role for Fgf but not Wnt in otic placode induction
Phillips, B. T., Storch, E. M., Lekven, A. C., & Riley, B. B. (2004) · Development · doi:10.1242/dev.00978 · Cited by 78 · see citing works
“It should be pointed out that one limitation of this transgene is that it reports only transcriptional activation by Lef1, a mediator of the canonical Wnt pathway, but it does not reflect signaling via the alternate Wnt mediators, Tcf3 and Tcf3b (Dorsky et al., 2002).”
BackgroundInfluentialPatterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl
Jeong, J., Einhorn, Z., Mathur, P., Chen, L., Lee, S., Kawakami, K., & Guo, S. (2006) · Development · doi:10.1242/dev.02705 · Cited by 77 · see citing works
“The hdl/tcf3 MO was synthesized according to published information (Dorsky et al., 2003), and 3-4 nl of 0.3 mM was used per embryo.”
MethodInfluentialNLK positively regulates Wnt/β‐catenin signalling by phosphorylating LEF1 in neural progenitor cells
Ota, S., Ishitani, S., Shimizu, N., Matsumoto, K., Itoh, M., & Ishitani, T. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.46 · Cited by 82 · see citing works
“…zebrafish line carrying a Wnt/ b -catenin signalling reporter construct (TOPdGFP), in which destabilized green fluorescent protein (dGFP) is driven by a promoter containing multiple TCF/LEF-binding sites, and thus indicates tissues where Lef1 is transcriptionally active (Dorsky et al , 2002).”
Generation and application of signaling pathway reporter lines in zebrafish
Moro, E., Vettori, A., Porazzi, P., Schiavone, M., Rampazzo, E., Casari, A., Ek, O., Facchinello, N., Astone, M., Zancan, I., et al. (2013) · Molecular Genetics and Genomics · doi:10.1007/s00438-013-0750-z · Cited by 76 · see citing works
“In agreement with this hypothesis, a direct comparison between two Wnt reporter lines, the TOPdGFP (Dorsky et al. 2002) and the more recent TCFsiam Tg(7xTCFX.lasiam:GFP)ia4 (Moro et al. 2012), has been recently addressed.”
BackgroundMethodInfluentialLi, S., Esterberg, R., Lachance, V., Ren, D., Radde‐Gallwitz, K., Chi, F., Parent, J., Fritz, A., & Chen, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013170108 · Cited by 74 · see citing works
“We also injected rack1 MO into a transgenic zebrafish line containing GFP under the control of a TOPFlash reporter [Tg (TOP:GFP)] (38) and obtained consistent data supporting that Rack1 is capable of inhibiting canonical Wnt target genes in vivo.”
MethodShiomi, K., UCHIDA, H., Keino‐Masu, K., & Masu, M. (2003) · Current Biology · doi:10.1016/s0960-9822(02)01398-2 · Cited by 74 · see citing works
Nicol, B., & Guiguen, Y. (2011) · Sexual Development · doi:10.1159/000334515 · Cited by 73 · see citing works
“, 2007], all members of the Tcf/Lef family are able to induce specific responses due to the complexity of their splicing and their differential expression [Dorsky et al., 2002; Gradl et al., 2002; Arce et al., 2006].”
BackgroundSrc- and confinement-dependent FAK activation causes E-cadherin relaxation and β-catenin activity
Gayrard, C., Bernaudin, C., Déjardin, T., Seiler, C., & Borghi, N. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201706013 · Cited by 73 · see citing works
“To assess whether this selective β-catenin nuclear accumulation was accompanied by an increase in its transcriptional activity, we used cells carrying the TOPdGFP sensor, which expresses destabilized GFP under the control of the LEF-1/TCF promoter (Dorsky et al., 2002; Maher et al., 2009).”
β‐Catenin in the Melanocyte Lineage
Larue, L., Kumasaka, M. Y., & Goding, C. R. (2003) · Pigment Cell Research · doi:10.1034/j.1600-0749.2003.00050.x · Cited by 72 · see citing works
Ramel, M., & Hill, C. S. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.03.003 · Cited by 71 · see citing works
- Authors
- Dorsky, R. I., Sheldahl, L. C., & Moon, R. T.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Moon, Randall T.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 241
- Issue
- 2
- Pages
- 229-237
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2165622092
- Cited by
- 287
- References
- 35
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 20 · 2014: 13 · 2013: 27 · 2012: 20
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- Wnt/β-catenin signaling, LEF1, TCF3, transgenic reporter, zebrafish embryonic development, Wnt1, forebrain development
- MeSH terms
- Animals, Binding Sites, Brain, Cytoskeletal Proteins, DNA-Binding Proteins, Embryo, Nonmammalian, Genes, Synthetic, Luminescent Proteins, Microinjections, Nerve Tissue Proteins, Pigment Epithelium of Eye, Promoter Regions, Genetic, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Tail, Transcription Factors, Transcription, Genetic, Zebrafish, Zygote, Trans-Activators, Genes, fos, Genes, Reporter, Gene Expression Regulation, Developmental, Body Patterning, Oligodeoxyribonucleotides, Antisense, HMGB Proteins, Zebrafish Proteins, Animals, Genetically Modified, Green Fluorescent Proteins, Wnt Proteins, Wnt1 Protein, beta Catenin, TCF Transcription Factors, Lymphoid Enhancer-Binding Factor 1, Transcription Factor 7-Like 1 Protein
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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