In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains

Enrico Moro; Gunes Ozhan-Kizil; Alessandro Mongera; Dimitris Beis; Claudia Wierzbicki; Rodrigo M. Young; Despina Bournele; Alice Domenichini; Leonardo E. Valdivia; Lawrence Lum; Chuo Chen; James F. Amatruda; Natascia Tiso; Gilbert Weidinger; Francesco Argenton

doi:10.1016/j.ydbio.2012.03.023

In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains

Enrico Moro, Gunes Ozhan-Kizil, Alessandro Mongera, Dimitris Beis, Claudia Wierzbicki, Rodrigo M. Young, Despina Bournele, Alice Domenichini, Leonardo E. Valdivia, Lawrence Lum, Chuo Chen, James F. Amatruda, Natascia Tiso, Gilbert Weidinger, Francesco Argenton

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

Abstract

The creation of molecular tools able to unravel in vivo spatiotemporal activation of specific cell signaling events during cell migration, differentiation and morphogenesis is of great relevance to developmental cell biology. Here, we describe the generation, validation and applications of two transgenic reporter lines for Wnt/Β-catenin signaling, named TCFsiam, and show that they are reliable and sensitive Wnt biosensors for in vivo studies. We demonstrate that these lines sensitively detect Wnt/Β-catenin pathway activity in several cellular contexts, from sensory organs to cardiac valve patterning. We provide evidence that Wnt/Β-catenin activity is involved in the formation and maintenance of the zebrafish CNS blood vessel network, on which sox10 neural crest-derived cells migrate and proliferate. We finally show that these transgenic lines allow for screening of Wnt signaling modifying compounds, tissue regeneration assessment as well as evaluation of potential Wnt/Β-catenin genetic modulators.

Original language	English (US)
Pages (from-to)	327-340
Number of pages	14
Journal	Developmental Biology
Volume	366
Issue number	2
DOIs	https://doi.org/10.1016/j.ydbio.2012.03.023
State	Published - Jun 15 2012

Keywords

Biosensor
Confocal microscopy
Reporter
Small-chemicals
Wnt/Β-catenin
Zebrafish

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.ydbio.2012.03.023

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Moro, E., Ozhan-Kizil, G., Mongera, A., Beis, D., Wierzbicki, C., Young, R. M., Bournele, D., Domenichini, A., Valdivia, L. E., Lum, L., Chen, C., Amatruda, J. F., Tiso, N., Weidinger, G., & Argenton, F. (2012). In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains. Developmental Biology, 366(2), 327-340. https://doi.org/10.1016/j.ydbio.2012.03.023

Moro, E, Ozhan-Kizil, G, Mongera, A, Beis, D, Wierzbicki, C, Young, RM, Bournele, D, Domenichini, A, Valdivia, LE, Lum, L , Chen, C, Amatruda, JF, Tiso, N, Weidinger, G & Argenton, F 2012, 'In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains', Developmental Biology, vol. 366, no. 2, pp. 327-340. https://doi.org/10.1016/j.ydbio.2012.03.023

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title = "In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains",

abstract = "The creation of molecular tools able to unravel in vivo spatiotemporal activation of specific cell signaling events during cell migration, differentiation and morphogenesis is of great relevance to developmental cell biology. Here, we describe the generation, validation and applications of two transgenic reporter lines for Wnt/Β-catenin signaling, named TCFsiam, and show that they are reliable and sensitive Wnt biosensors for in vivo studies. We demonstrate that these lines sensitively detect Wnt/Β-catenin pathway activity in several cellular contexts, from sensory organs to cardiac valve patterning. We provide evidence that Wnt/Β-catenin activity is involved in the formation and maintenance of the zebrafish CNS blood vessel network, on which sox10 neural crest-derived cells migrate and proliferate. We finally show that these transgenic lines allow for screening of Wnt signaling modifying compounds, tissue regeneration assessment as well as evaluation of potential Wnt/Β-catenin genetic modulators.",

keywords = "Biosensor, Confocal microscopy, Reporter, Small-chemicals, Wnt/Β-catenin, Zebrafish",

author = "Enrico Moro and Gunes Ozhan-Kizil and Alessandro Mongera and Dimitris Beis and Claudia Wierzbicki and Young, {Rodrigo M.} and Despina Bournele and Alice Domenichini and Valdivia, {Leonardo E.} and Lawrence Lum and Chuo Chen and Amatruda, {James F.} and Natascia Tiso and Gilbert Weidinger and Francesco Argenton",

note = "Funding Information: We thank Prof. Stefano Piccolo (University of Padova) for kindly providing the BAT-lux construct and helpful advice and Steve Wilson for the lef1/sinf U767 mutant. This work is supported by CARIPARO “Cancer biosensors” and AIRC IG10274 grants to FA, by the EU grants ZF-HEALTH Large-scale Integrated Project in the 7th Framework Program (Grant Agreement 242048-2) to FA and NT, by a University of Padova Grant (Contract n.CPDA089044) to NT, by the Human Frontier Science Program Organization (CDA to DB), by the Deutsche Forschungsgemeinshaft through the DFG-Center for Regenerative Therapies Dresden (CRTD)/Cluster of Excellence and Biotechnologies Center to GW and partly by the Italian Ministry of Health (Grant GR-2008–1139743) to EM. ",

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doi = "10.1016/j.ydbio.2012.03.023",

language = "English (US)",

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AU - Moro, Enrico

AU - Ozhan-Kizil, Gunes

AU - Mongera, Alessandro

AU - Beis, Dimitris

AU - Wierzbicki, Claudia

AU - Young, Rodrigo M.

AU - Bournele, Despina

AU - Domenichini, Alice

AU - Valdivia, Leonardo E.

AU - Lum, Lawrence

AU - Chen, Chuo

AU - Amatruda, James F.

AU - Tiso, Natascia

AU - Weidinger, Gilbert

AU - Argenton, Francesco

N1 - Funding Information: We thank Prof. Stefano Piccolo (University of Padova) for kindly providing the BAT-lux construct and helpful advice and Steve Wilson for the lef1/sinf U767 mutant. This work is supported by CARIPARO “Cancer biosensors” and AIRC IG10274 grants to FA, by the EU grants ZF-HEALTH Large-scale Integrated Project in the 7th Framework Program (Grant Agreement 242048-2) to FA and NT, by a University of Padova Grant (Contract n.CPDA089044) to NT, by the Human Frontier Science Program Organization (CDA to DB), by the Deutsche Forschungsgemeinshaft through the DFG-Center for Regenerative Therapies Dresden (CRTD)/Cluster of Excellence and Biotechnologies Center to GW and partly by the Italian Ministry of Health (Grant GR-2008–1139743) to EM.

PY - 2012/6/15

Y1 - 2012/6/15

N2 - The creation of molecular tools able to unravel in vivo spatiotemporal activation of specific cell signaling events during cell migration, differentiation and morphogenesis is of great relevance to developmental cell biology. Here, we describe the generation, validation and applications of two transgenic reporter lines for Wnt/Β-catenin signaling, named TCFsiam, and show that they are reliable and sensitive Wnt biosensors for in vivo studies. We demonstrate that these lines sensitively detect Wnt/Β-catenin pathway activity in several cellular contexts, from sensory organs to cardiac valve patterning. We provide evidence that Wnt/Β-catenin activity is involved in the formation and maintenance of the zebrafish CNS blood vessel network, on which sox10 neural crest-derived cells migrate and proliferate. We finally show that these transgenic lines allow for screening of Wnt signaling modifying compounds, tissue regeneration assessment as well as evaluation of potential Wnt/Β-catenin genetic modulators.

AB - The creation of molecular tools able to unravel in vivo spatiotemporal activation of specific cell signaling events during cell migration, differentiation and morphogenesis is of great relevance to developmental cell biology. Here, we describe the generation, validation and applications of two transgenic reporter lines for Wnt/Β-catenin signaling, named TCFsiam, and show that they are reliable and sensitive Wnt biosensors for in vivo studies. We demonstrate that these lines sensitively detect Wnt/Β-catenin pathway activity in several cellular contexts, from sensory organs to cardiac valve patterning. We provide evidence that Wnt/Β-catenin activity is involved in the formation and maintenance of the zebrafish CNS blood vessel network, on which sox10 neural crest-derived cells migrate and proliferate. We finally show that these transgenic lines allow for screening of Wnt signaling modifying compounds, tissue regeneration assessment as well as evaluation of potential Wnt/Β-catenin genetic modulators.

KW - Biosensor

KW - Confocal microscopy

KW - Reporter

KW - Small-chemicals

KW - Wnt/Β-catenin

KW - Zebrafish

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EP - 340

JO - Developmental Biology

JF - Developmental Biology

IS - 2

ER -

In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains

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