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ZFIN ID: ZDB-LAB-980505-1
Raz Lab
PI/Director: Raz, Erez
Co-PI / Senior
Reichman-Fried, Michal
Tarbashevich, Katsiyarina
Contact Person: Raz, Erez
Address: Institute of Cell Biology Center for Molecular Biology of Inflammation Von-Esmarchstr. 56 D-48149 Muenster
Country: Germany
Phone: 49-251-8358617
Fax: 49-251-8358616
Line Designation: mu

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Primordial Germ Cells (PGCs) of zebrafish originate at random positions with respect to the dorsoventral axis. Yet, within 24 hours of development most of the cells arrive at distinct bilateral positions from which they coalesce into a gonad. We use zebrafish PGCs as model for cell fate specification, motility and directed migration in-vivo 3D environment. Different research lines in each area are under investigation.

* Cell fate specification

To learn more about the molecular mechanisms of PGC specification in zebrafish, we initiated screens for genes that are expressed in the germ cells at different time points during early embryogenesis. Results of In-Situ hybridization screens, Microarray data and next generation sequencing were combined to highlight the most crucial players in PGCs specification. Functional analysis of these genes are being investigated using different genetic approaches including morpholino knock-down assays as well as knock-out generation using Zinc finger nucleases (ZFNs) and TALENs.
For example, morphant embryos for Dead End (Dnd - maternally provided germ plasm component) loose their PGCs through Apoptosis by the end of first day of development. We found that Dnd functions by protecting specific mRNAs from microRNA inhibitory effects. We set to find protein interaction partners of Dnd as well as protected mRNAs, to understand the molecular basis of fate specification and maintenance in zebrafish PGCs.

* Motility

Zebrafish PGCs produce protrusions in the form of blebs during their migration. This is intrinsic behavior of PGCs and independent of external guiding cue. We would like to understand the basis for this type of motility.
Several projects in the lab use genetic and biophysical approaches to investigate mechanisms of bleb formation in PGCs, characteristics of germ cells blebs and their actual contribution to cell motility.
The nature and coordination of forces inside and outside of motile germ cells including internal pressure, differential contractile forces and regulation of adhesiveness to neighboring cells are among other projects, which are currently under investigation in our lab.

* Directed migration

We have previously identified the attractive signal for germ cell directed migration as the chemokine Cxcl12a.
PGCs migrate along the gradient of Cxcl12a that is detected by the Cxcr4b receptor expressed in the PGCs. The distribution of Cxcl12a is dynamically shaped by a decoy receptor CXCR7 expressed in somatic cells.
We are currently investigating the molecular signaling cascade downstream of CXCR4b and mechanisms of gradient sensing by PGCs.

Gross-Thebing, Sargon Graduate Student Hoffmann, Dennis Graduate Student Labbaf, Zahra Graduate Student
Limon Tejeda, Tamara Graduate Student Olguin-Olguin, Adan Graduate Student Ophaus, Moritz Graduate Student
Truszkowski, Lukasz Graduate Student Westerich, Kim Graduate Student Jordan, Ursula Technical Staff
Messerschmidt, Esther-Maria Technical Staff Sandbote, Ines Technical Staff Glaesner, Gabriele Administrative Staff

Bertho, S., Clapp, M., Banisch, T.U., Bandemer, J., Raz, E., Marlow, F.L. (2021) Zebrafish dazl regulates cystogenesis and germline stem cell specification during the primordial germ cell to germline stem cell transition. Development (Cambridge, England). 148(7):
Dirks, C., Striewski, P., Wirth, B., Aalto, A., Olguin-Olguin, A. (2021) A mathematical model for bleb regulation in zebrafish primordial germ cells. Mathematical medicine and biology : a journal of the IMA. 38(2):218-254
Olguin-Olguin, A., Aalto, A., Maugis, B., Boquet-Pujadas, A., Hoffmann, D., Ermlich, L., Betz, T., Gov, N.S., Reichman-Fried, M., Raz, E. (2021) Chemokine-biased robust self-organizing polarization of migrating cells in vivo. Proceedings of the National Academy of Sciences of the United States of America. 118(7):
Gross-Thebing, S., Truszkowski, L., Tenbrinck, D., Sánchez-Iranzo, H., Camelo, C., Westerich, K.J., Singh, A., Maier, P., Prengel, J., Lange, P., Hüwel, J., Gaede, F., Sasse, R., Vos, B.E., Betz, T., Matis, M., Prevedel, R., Luschnig, S., Diz-Muñoz, A., Burger, M., Raz, E. (2020) Using migrating cells as probes to illuminate features in live embryonic tissues. Science advances. 6(49):
Grimaldi, C., Schumacher, I., Boquet-Pujadas, A., Tarbashevich, K., Vos, B.E., Bandemer, J., Schick, J., Aalto, A., Olivo-Marin, J.C., Betz, T., Raz, E. (2020) E-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow. Nature communications. 11:5397
Westerich, K.J., Chandrasekaran, K.S., Gross-Thebing, T., Kueck, N., Raz, E., Rentmeister, A. (2020) Bioorthogonal mRNA labeling at the poly(A) tail for imaging localization and dynamics in live zebrafish embryos. Chemical science. 11:3089-3095
Lavi, I., Goudarzi, M., Raz, E., Gov, N.S., Voituriez, R., Sens, P. (2019) Cellular Blebs and Membrane Invaginations Are Coupled through Membrane Tension Buffering. Biophysical journal. 117:1485-1495
Skvortsova, K., Tarbashevich, K., Stehling, M., Lister, R., Irimia, M., Raz, E., Bogdanovic, O. (2019) Retention of paternal DNA methylome in the developing zebrafish germline. Nature communications. 10:3054
Goudarzi, M., Boquet-Pujadas, A., Olivo-Marin, J.C., Raz, E. (2019) Fluid dynamics during bleb formation in migrating cells in vivo. PLoS One. 14:e0212699
Malhotra, D., Shin, J., Solnica-Krezel, L., Raz, E. (2018) Spatio-temporal regulation of concurrent developmental processes by generic signaling downstream of chemokine receptors. eLIFE. 7
Pfeiffer, J., Tarbashevich, K., Bandemer, J., Palm, T., Raz, E. (2018) Rapid progression through the cell cycle ensures efficient migration of primordial germ cells - the role of Hsp90. Developmental Biology. 436(2):84-93
Gross-Thebing, T., Yigit, S., Pfeiffer, J., Reichman-Fried, M., Bandemer, J., Ruckert, C., Rathmer, C., Goudarzi, M., Stehling, M., Tarbashevich, K., Seggewiss, J., Raz, E. (2017) The Vertebrate Protein Dead End Maintains Primordial Germ Cell Fate by Inhibiting Somatic Differentiation. Developmental Cell. 43:704-715.e5
Goudarzi, M., Tarbashevich, K., Mildner, K., Begemann, I., Garcia, J., Paksa, A., Reichman-Fried, M., Mahabaleshwar, H., Blaser, H., Hartwig, J., Zeuschner, D., Galic, M., Bagnat, M., Betz, T., Raz, E. (2017) Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations. Developmental Cell. 43(5):577-587.e5
Hörner, F., Meissner, R., Polali, S., Pfeiffer, J., Betz, T., Denz, C., Raz, E. (2017) Holographic optical tweezers-based in vivo manipulations in zebrafish embryos. Journal of biophotonics. 10(11):1492-1501
Stainier, D.Y.R., Raz, E., Lawson, N.D., Ekker, S.C., Burdine, R.D., Eisen, J.S., Ingham, P.W., Schulte-Merker, S., Yelon, D., Weinstein, B.M., Mullins, M.C., Wilson, S.W., Ramakrishnan, L., Amacher, S.L., Neuhauss, S.C.F., Meng, A., Mochizuki, N., Panula, P., Moens, C.B. (2017) Guidelines for morpholino use in zebrafish. PLoS Genetics. 13:e1007000
Otten, A.B., Theunissen, T.E., Derhaag, J.G., Lambrichs, E.H., Boesten, I.B., Winandy, M., van Montfoort, A.P., Tarbashevich, K., Raz, E., Gerards, M., Vanoevelen, J.M., van den Bosch, B.J., Muller, M., Smeets, H.J. (2016) Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells. Cell Reports. 16(3):622-30
Paksa, A., Bandemer, J., Hoeckendorf, B., Razin, N., Tarbashevich, K., Minina, S., Meyen, D., Biundo, A., Leidel, S.A., Peyrieras, N., Gov, N.S., Keller, P.J., Raz, E. (2016) Repulsive cues combined with physical barriers and cell-cell adhesion determine progenitor cell positioning during organogenesis. Nature communications. 7:11288
Reichman-Fried, M., Raz, E. (2016) Blood, blebs and lumen expansion. Nature cell biology. 18:366-7
Tulotta, C., Stefanescu, C., Beletkaia, E., Bussmann, J., Tarbashevich, K., Schmidt, T., Snaar-Jagalska, B.E. (2016) Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model. Disease models & mechanisms. 9(2):141-53
Goudarzi, M., Mildner, K., Babatz, F., Riedel, D., Klämbt, C., Zeuschner, D., Raz, E. (2015) Correlative Light and Electron Microscopy of Rare Cell Populations in Zebrafish Embryos Using Laser Marks. Zebrafish. 12(6):470-3
Paksa, A., Raz, E. (2015) Zebrafish germ cells: motility and guided migration. Current opinion in cell biology. 36:80-85
Bussmann, J., Raz, E. (2015) Chemokine-guided cell migration and motility in zebrafish development. The EMBO journal. 34(10):1309-1318
Tarbashevich, K., Reichman-Fried, M., Grimaldi, C., Raz, E. (2015) Chemokine-Dependent pH Elevation at the Cell Front Sustains Polarity in Directionally Migrating Zebrafish Germ Cells. Current biology : CB. 25(8):1096-103
Meyen, D., Tarbashevich, K., Banisch, T.U., Wittwer, C., Reichman-Fried, M., Maugis, B., Grimaldi, C., Messerschmidt, E.M., Raz, E. (2015) Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo. eLIFE. 4
Stanganello, E., Hagemann, A.I., Mattes, B., Sinner, C., Meyen, D., Weber, S., Schug, A., Raz, E., Scholpp, S. (2015) Filopodia-based Wnt transport during vertebrate tissue patterning. Nature communications. 6:5846
Xu, C., Hasan, S.S., Schmidt, I., Rocha, S.F., Pitulescu, M.E., Bussmann, J., Meyen, D., Raz, E., Adams, R.H., Siekmann, A.F. (2014) Arteries are formed by vein-derived endothelial tip cells. Nature communications. 5:5758
Gross-Thebing, T., Paksa, A., Raz, E. (2014) Simultaneous high-resolution detection of multiple transcripts combined with localization of proteins in whole-mount embryos. BMC Biology. 12:55
Hartwig, J., Tarbashevich, K., Seggewiß, J., Stehling, M., Bandemer, J., Grimaldi, C., Paksa, A., Groß-Thebing, T., Meyen, D., Raz, E. (2014) Temporal control over the initiation of cell motility by a regulator of G-protein signaling. Proceedings of the National Academy of Sciences of the United States of America. 111(31):11389-94
Dalle Nogare, D., Somers, K., Rao, S., Matsuda, M., Reichman-Fried, M., Raz, E., Chitnis, A.B. (2014) Leading and trailing cells cooperate in collective migration of the zebrafish Posterior Lateral Line primordium. Development (Cambridge, England). 141(16):3188-96
Reichman-Fried, M., Raz, E. (2014) Small proteins, big roles: The signaling protein Apela extends the complexity of developmental pathways in the early zebrafish embryo. BioEssays : news and reviews in molecular, cellular and developmental biology. 36(8):741-5
Goudarzi, M., Strate, I., Paksa, A., Lagendijk, A.K., Bakkers, J., and Raz, E. (2013) On the robustness of germ cell migration and microRNA-mediated regulation of chemokine signaling. Nature Genetics. 45(11):1264-1265
Paluch, E.K., and Raz, E. (2013) The role and regulation of blebs in cell migration. Current opinion in cell biology. 25(5):582-590
Mahabaleshwar, H., Tarbashevich, K., Nowak, M., Brand, M., and Raz, E. (2012) beta-arrestin control of late endosomal sorting facilitates decoy receptor function and chemokine gradient formation. Development (Cambridge, England). 139(16):2897-2902
Stückemann, T., Wegleiter, T., Stefan, E., Nägele, O., Tarbashevich, K., Böck, G., Raz, E., and Aanstad, P. (2012) Zebrafish Cxcr4a determines the proliferative response to Hedgehog signalling. Development (Cambridge, England). 139(15):2711-2720
Goudarzi, M., Banisch, T.U., Mobin, M.B., Maghelli, N., Tarbashevich, K., Strate, I., van den Berg, J., Blaser, H., Bandemer, S., Paluch, E., Bakkers, J., Toli-Nørrelykke, I.M., and Raz, E. (2012) Identification and Regulation of a Molecular Module for Bleb-Based Cell Motility. Developmental Cell. 23(1):210-218
Xu, H., Kardash, E., Chen, S., Raz, E., and Lin, F. (2012) Gβγ signaling controls the polarization of zebrafish primordial germ cells by regulating Rac activity. Development (Cambridge, England). 139(1):57-62
Kardash, E., Bandemer, J., and Raz, E. (2011) Imaging protein activity in live embryos using fluorescence resonance energy transfer biosensors. Nature Protocols. 6(12):1835-1846
Boldajipour, B., Doitsidou, M., Tarbashevich, K., Laguri, C., Yu, S.R., Ries, J., Dumstrei, K., Thelen, S., Dörries, J., Messerschmidt, E.M., Thelen, M., Schwille, P., Brand, M., Lortat-Jacob, H., and Raz, E. (2011) Cxcl12 evolution - subfunctionalization of a ligand through altered interaction with the chemokine receptor. Development (Cambridge, England). 138(14):2909-2914
Mickoleit, M., Banisch, T.U., and Raz, E. (2011) Regulation of hub mRNA stability and translation by miR430 and the dead end protein promotes preferential expression in zebrafish primordial germ cells. Developmental dynamics : an official publication of the American Association of Anatomists. 240(3):695-703
Koebernick, K., Loeber, J., Arthur, P.K., Tarbashevich, K., and Pieler, T. (2010) Elr-type proteins protect Xenopus Dead end mRNA from miR-18-mediated clearance in the soma. Proceedings of the National Academy of Sciences of the United States of America. 107(37):16148-16153
Naumann, U., Cameroni, E., Pruenster, M., Mahabaleshwar, H., Raz, E., Zerwes, H.G., Rot, A., and Thelen, M. (2010) CXCR7 Functions as a Scavenger for CXCL12 and CXCL11. PLoS One. 5(2):e9175
Mulligan, T., Blaser, H., Raz, E., and Farber, S.A. (2010) Prenylation-deficient G protein gamma subunits disrupt GPCR signaling in the zebrafish. Cellular Signalling. 22(2):221-233
Kardash, E., Reichman-Fried, M., Maître, J.L., Boldajipour, B., Papusheva, E., Messerschmidt, E.M., Heisenberg, C.P., and Raz, E. (2010) A role for Rho GTPases and cell-cell adhesion in single-cell motility in vivo. Nature cell biology. 12(1):47-53
Stolp, B., Reichman-Fried, M., Abraham, L., Pan, X., Giese, S.I., Hannemann, S., Goulimari, P., Raz, E., Grosse, R., and Fackler, O.T. (2009) HIV-1 Nef Interferes with Host Cell Motility by Deregulation of Cofilin. Cell Host & Microbe. 6(2):174-186
Mich, J.K., Blaser, H., Thomas, N.A., Firestone, A.J., Yelon, D., Raz, E., and Chen, J.K. (2009) Germ cell migration in zebrafish is cyclopamine-sensitive but Smoothened-independent. Developmental Biology. 328(2):342-354
Raz, E., and Mahabaleshwar, H. (2009) Chemokine signaling in embryonic cell migration: a fisheye view. Development (Cambridge, England). 136(8):1223-1229
Slanchev, K., Stebler, J., Goudarzi, M., Cojocaru, V., Weidinger, G., and Raz, E. (2009) Control of Dead end localization and activity – Implications for the function of the protein in antagonizing miRNA function. Mechanisms of Development. 126(3-4):270-277
Herpin, A., Fischer, P., Liedtke, D., Kluever, N., Neuner, C., Raz, E., and Schartl, M. (2008) Sequential SDF1a and b-induced mobility guides Medaka PGC migration. Developmental Biology. 320(2):319-327
Strasser, M.J., Mackenzie, N.C., Dumstrei, K., Nakkrasae, L.I., Stebler, J., and Raz, E. (2008) Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development. BMC Developmental Biology. 8:58
Mahabaleshwar, H., Boldajipour, B., and Raz, E. (2008) Killing the messenger: The role of CXCR7 in regulating primordial germ cell migration. Cell adhesion & migration. 2(2):69-70
Boldajipour, B., Mahabaleshwar, H., Kardash, E., Reichman-Fried, M., Blaser, H., Minina, S., Wilson, D., Xu, Q., and Raz, E. (2008) Control of chemokine-guided cell migration by ligand sequestration. Cell. 132(3):463-473
Kedde, M., Strasser, M.J., Boldajipour, B., Oude Vrielink, J.A., Slanchev, K., le Sage, C., Nagel, R., Voorhoeve, P.M., van Duijse, J., Andersson Ørom, U., Lund, A.H., Perrakis, A., Raz, E., and Agami, R. (2007) RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA. Cell. 131(7):1273-1286
Minina, S., Reichman-Fried, M., and Raz, E. (2007) Control of receptor internalization, signaling level, and precise arrival at the target in guided cell migration. Current biology : CB. 17(13):1164-1172
Houwing, S., Kamminga, L.M., Berezikov, E., Cronembold, D., Girard, A., van den Elst, H., Filippov, D.V., Blaser, H., Raz, E., Moens, C.B., Plasterk, R.H., Hannon, G.J., Draper, B.W., and Ketting, R.F. (2007) A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell. 129(1):69-82
Blaser, H., Reichman-Fried, M., Castanon, I., Dumstrei, K., Marlow, F.L., Kawakami, K., Solnica-Krezel, L., Heisenberg, C.P., and Raz, E. (2006) Migration of zebrafish primordial germ cells: a role for Myosin contraction and cytoplasmic flow. Developmental Cell. 11(5):613-627
Raz, E., and Reichman-Fried, M. (2006) Attraction rules: germ cell migration in zebrafish. Current opinion in genetics & development. 16(4):355-359
Blaser, H., Eisenbeiss, S., Neumann, M., Reichman-Fried, M., Thisse, B., Thisse, C., and Raz, E. (2005) Transition from non-motile behaviour to directed migration during early PGC development in zebrafish. Journal of Cell Science. 118(17):4027-4038
Slanchev, K., Stebler, J., de la Cueva-Mendez, G., and Raz, E. (2005) Development without germ cells: The role of the germ line in zebrafish sex differentiation. Proceedings of the National Academy of Sciences of the United States of America. 102(11):4074-4079
Dumstrei, K., Mennecke, R., and Raz, E. (2004) Signaling pathways controlling primordial germ cell migration in zebrafish. Journal of Cell Science. 117(Pt20):4787-4795
Spieler, D., Bäumer, N., Stebler, J., Köprunner, M., Reichman-Fried, M., Teichmann, U., Raz, E., Kessel, M., and Wittler, L. (2004) Involvement of Pax6 and Otx2 in the forebrain-specific regulation of the vertebrate homeobox gene ANF/Hesx1. Developmental Biology. 269(2):567-579
Raz, E. (2004) Guidance of primordial germ cell migration. Current opinion in cell biology. 16(2):169-173
Reichman-Fried, M., Minina, S., and Raz, E. (2004) Autonomous modes of behavior in primordial germ cell migration. Developmental Cell. 6(4):589-596
Thorpe, J.L., Doitsidou, M., Ho, S.-Y., Raz, E., and Farber, S.A. (2004) Germ Cell Migration in Zebrafish Is Dependent on HMGCoA Reductase Activity and Prenylation. Developmental Cell. 6:5-302
Molyneaux, K.A., Zinszner, H., Kunwar, P.S., Schaible, K., Stebler, J., Sunshine, M.J., O'Brien, W., Raz, E., Littman, D., Wylie, C., and Lehmann, R. (2003) The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development (Cambridge, England). 130(18):4279-4286
Raz, E. (2003) Primordial germ-cell development: the zebrafish perspective. Nature reviews. Genetics. 4(9):690-700
Weidinger, G., Stebler, J., Slanchev, K., Dumstrei, K., Wise, C., Lovell-Badge, R., Thisse, C., Thisse, B., and Raz, E. (2003) dead end, a novel vertebrate germ plasm component, is required for zebrafish primordial germ cell migration and survival. Current biology : CB. 13(16):1429-1434
Raz, E. (2002) Primordial germ cell development in zebrafish. Seminars in cell & developmental biology. 13:489-495
Doitsidou, M., Reichman-Fried, M., Stebler, J., Köprunner, M., Dörries, J., Meyer, D., Esguerra, C.V., Leung, T., and Raz, E. (2002) Guidance of primordial germ cell migration by the chemokine SDF-1. Cell. 111(5):647-659
Ciruna, B., Weidinger, G., Knaut, H., Thisse, B., Thisse, C., Raz, E., and Schier, A.F. (2002) Production of maternal-zygotic mutant zebrafish by germ-line replacement. Proceedings of the National Academy of Sciences of the United States of America. 99(23):14919-14924
Müller, K., Thisse, C., Thisse, B. and Raz, E. (2002) Expression of a linker histone-like gene in the primordial germ cells in zebrafish. Mechanisms of Development. 117:253-257
Wolke, U., Weidinger, G., Köprunner, M., and Raz, E. (2002) Multiple levels of post-transcriptional control lead to germ line specific gene expression in the zebrafish. Current biology : CB. 12(4):289-294
Raz, E. and Hopkins, N. (2002) Primordial germ-cell development in zebrafish. Results and problems in cell differentiation. 40:166-179
Weidinger, G., Wolke, U., Köprunner, M., Thisse, C., Thisse, B. and Raz, E. (2002) Regulation of zebrafish primordial germ cell migration by attraction towards an intermediate target. Development (Cambridge, England). 129:25-36
Köprunner, M., Thisse, C., Thisse, B., and Raz, E. (2001) A zebrafish nanos related gene is essential for the development of primordial germ cells. Genes & Development. 15(21):2877-2885
Weidinger, G., Koprunner, M., Wolke, U., Thisse, C., Thisse, B., and Raz, E. (2001) Attraction, active migration, and clustering of zebrafish primordial germ cells. Developmental Biology. 235(1):175 (#18)
Raz, E. (2000) The function and regulation of vasa-like genes in germ-cell development. Genome biology. 1(3):1017
Weidinger, G., Wolke, U., Köprunner, M., Klinger, M., and Raz, E. (1999) Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells. Development (Cambridge, England). 126(23):5295-5307
Zhang, Q., Yaniv, K., Oberman, F., Wolke, U., Git, A., Fromer, M., Taylor, W.L., Meyer, D., Standart, N., Raz, E., and Yisraeli, J.K. (1999) Vg1 RBP intracellular distribution and evolutionarily conserved expression at multiple stages during development. Mechanisms of Development. 88(1):101-106
Raz, E., Zlokarnik, G., Tsien, R.Y., and Driever, W. (1998) ß-lactamase as a marker for gene expression in live zebrafish embryos. Developmental Biology. 203:290-294
Raz, E., Van Luenen, H.G.A.M., Schaerringer, B., Plasterk, R.H.A., and Driever, W. (1998) Transposition of the nematode Caenorhabditis elegans Tc3 element in the zebrafish Danio rerio. Current biology : CB. 8:82-88
Moss, J.B., Price, A.L., Raz, E., Driever, W., and Rosenthal, N. (1996) Green fluorescent protein marks skeletal muscle in murine cell lines and zebrafish. Gene. 173:89-98