Bernard V. Thisse
- Email: bernardthisse@virginia.edu
- Phone: 434 243 6613
Primary Appointment
Professor, Cell Biology
Education
- PhD, Molecular Genetics, University of Strasbourg
- Postdoc, Developmental Biology, IGBMC_CNRS
- Postdoc, Developmental Biology, University of Oregon
Research Disciplines
Cell and Developmental Biology
Research Interests
Molecular control of embryonic development
Research Description
Previous work of our lab has focused on the establishment of the dorso-ventral axis of the zebrafish embryo through the regulation of the activity of TGFbeta superfamily members, the Bone Morphogenetic Proteins (BMPs), by specific secreted antagonists and by the Fibroblast growth factors (FGFs) signaling pathway that regulates BMP signal transduction.
We also established that factors belonging to another group of the TGFbeta superfamily, the Nodal related factors, are patterning the embryo along the animal-vegetal axis therefore controlling the establishment of the definitive antero-posterior axis of the embryo.
Looking at interactions between these signaling pathways, we found that specific combinations of BMP and Nodal signaling can induce the different domain of the embryo, posterior head, trunk or tail, present along the antero-posterior axis. Finally we discovered that a complete embryonic axis, with all proper tissues and organs can be organized by instructing uncommitted pluripotent embryonic cells with two opposing gradients of BMP and of Nodal that generate the full spectrum of combination of these two signals.
Because the signaling pathways controlling early embryonic development have been conserved across evolution we predict that results obtained using zebrafish embryonic cells can be extrapolated to mammalian embryos. Therefore we are now trying to take control of aggregates of mouse embryonic stem cells (embryoid bodies), instructing them through experimentally engineered, spatially defined, morphogen gradients that should control fate and behavior of these pluripotent cells. Our ultimate goal is to use this approach to generate functional tissues and organs for application in Regenerative Medicine.
In parallel to this study, our lab is investigating the role of the Hippo signaling pathway in the control of early embryonic development. Hippo is a highly conserved pathway known to control organ size through the regulation of cell proliferation, cell death and cell differentiation. We recently discovered an unsuspected role for the transcriptional mediators of the Hippo pathway (YAP, TAZ, TEADs) and their regulators (VGL4s) in the control, at the transcriptional level, of the formation of the ciliated organ that acts as the Left-Right organizer of the embryo. Using Crispr/Cas9 editing technology as well as various methods of gain of function and of gene knockdowns we are dissecting the molecular mechanisms regulating the formation of the Left-Right organizer and through a comprehensive analysis of the transcriptome of the precursor cells of the Left-Right organizer in the different loss of function conditions we are characterizing the cascade of gene products involved in the formation and function of this organ.
Selected Publications
Thisse B, Thisse C, Formation of the vertebrate embryo: Moving beyond the Spemann organizer., 2015; Seminars in cell & developmental biology. () . PMID: 25999320
Lu FI, Sun YH, Wei CY, Thisse C, Thisse B, Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway., 2014; Nature communications. 5() 5368. PMID: 25371059
Xu PF, Houssin N, Ferri-Lagneau KF, Thisse B, Thisse C, Construction of a vertebrate embryo from two opposing morphogen gradients., 2014; Science (New York, N.Y.). 344(6179) 87-9. PMID: 24700857
Lu FI, Thisse C, Thisse B, Identification and mechanism of regulation of the zebrafish dorsal determinant., 2011; Proceedings of the National Academy of Sciences of the United States of America. 108(38) 15876-80. PMID: 21911385 | PMCID: PMC3179059
Dal-Pra S, Thisse C, Thisse B, FoxA transcription factors are essential for the development of dorsal axial structures., 2010; Developmental biology. 350(2) 484-95. PMID: 21172337
Fauny JD, Thisse B, Thisse C, The entire zebrafish blastula-gastrula margin acts as an organizer dependent on the ratio of Nodal to BMP activity., 2009; Development (Cambridge, England). 136(22) 3811-9. PMID: 19855023
Thisse C, Thisse B, High-resolution in situ hybridization to whole-mount zebrafish embryos., 2008; Nature protocols. 3(1) 59-69. PMID: 18193022
Bertrand S, Thisse B, Tavares R, Sachs L, Chaumot A, Bardet PL, Escrivà H, Duffraisse M, Marchand O, Safi R, Thisse C, Laudet V, Unexpected novel relational links uncovered by extensive developmental profiling of nuclear receptor expression., 2007; PLoS genetics. 3(11) e188. PMID: 17997606 | PMCID: PMC2065881
Huang H, Lu FI, Jia S, Meng S, Cao Y, Wang Y, Ma W, Yin K, Wen Z, Peng J, Thisse C, Thisse B, Meng A, Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation., 2007; Development (Cambridge, England). 134(5) 979-88. PMID: 17293535
Deniziak M, Thisse C, Rederstorff M, Hindelang C, Thisse B, Lescure A, Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo., 2006; Experimental cell research. 313(1) 156-67. PMID: 17123513
Dal-Pra S, Fürthauer M, Van-Celst J, Thisse B, Thisse C, Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP activity., 2006; Developmental biology. 298(2) 514-26. PMID: 16890217
Poulain M, Fürthauer M, Thisse B, Thisse C, Lepage T, Zebrafish endoderm formation is regulated by combinatorial Nodal, FGF and BMP signalling., 2006; Development (Cambridge, England). 133(11) 2189-200. PMID: 16672336
Thisse B, Thisse C, Functions and regulations of fibroblast growth factor signaling during embryonic development., 2005; Developmental biology. 287(2) 390-402. PMID: 16216232
Seiliez I, Thisse B, Thisse C, FoxA3 and goosecoid promote anterior neural fate through inhibition of Wnt8a activity before the onset of gastrulation., 2005; Developmental biology. 290(1) 152-63. PMID: 16364286
Fürthauer M, Van Celst J, Thisse C, Thisse B, Fgf signalling controls the dorsoventral patterning of the zebrafish embryo., 2004; Development (Cambridge, England). 131(12) 2853-64. PMID: 15151985
Thisse B, Heyer V, Lux A, Alunni V, Degrave A, Seiliez I, Kirchner J, Parkhill JP, Thisse C, Spatial and temporal expression of the zebrafish genome by large-scale in situ hybridization screening., 2004; Methods in cell biology. 77() 505-19. PMID: 15602929
Delaunay F, Thisse C, Thisse B, Laudet V, Differential regulation of Period 2 and Period 3 expression during development of the zebrafish circadian clock., 2003; Gene expression patterns : GEP. 3(3) 319-24. PMID: 12799078
Agathon A, Thisse C, Thisse B, The molecular nature of the zebrafish tail organizer., 2003; Nature. 424(6947) 448-52. PMID: 12879074
Weidinger G, Stebler J, Slanchev K, Dumstrei K, Wise C, Lovell-Badge R, Thisse C, Thisse B, Raz E, dead end, a novel vertebrate germ plasm component, is required for zebrafish primordial germ cell migration and survival., 2003; Current biology : CB. 13(16) 1429-34. PMID: 12932328
Fürthauer M, Lin W, Ang SL, Thisse B, Thisse C, Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling., 2002; Nature cell biology. 4(2) 170-4. PMID: 11802165
Weidinger G, Wolke U, Köprunner M, Thisse C, Thisse B, Raz E, Regulation of zebrafish primordial germ cell migration by attraction towards an intermediate target., 2002; Development (Cambridge, England). 129(1) 25-36. PMID: 11782398
Herbomel P, Thisse B, Thisse C, Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through a M-CSF receptor-dependent invasive process., 2002; Developmental biology. 238(2) 274-88. PMID: 11784010
Kikuchi Y, Agathon A, Alexander J, Thisse C, Waldron S, Yelon D, Thisse B, Stainier DY, casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish., 2001; Genes & development. 15(12) 1493-505. PMID: 11410530 | PMCID: PMC312713
Köprunner M, Thisse C, Thisse B, Raz E, A zebrafish nanos-related gene is essential for the development of primordial germ cells., 2001; Genes & development. 15(21) 2877-85. PMID: 11691838 | PMCID: PMC312811
Fürthauer M, Reifers F, Brand M, Thisse B, Thisse C, sprouty4 acts in vivo as a feedback-induced antagonist of FGF signaling in zebrafish., 2001; Development (Cambridge, England). 128(12) 2175-86. PMID: 11493538
Agathon A, Thisse B, Thisse C, Morpholino knock-down of antivin1 and antivin2 upregulates nodal signaling., 2001; Genesis (New York, N.Y. : 2000). 30(3) 178-82. PMID: 11477702
Schmid B, Fürthauer M, Connors SA, Trout J, Thisse B, Thisse C, Mullins MC, Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation., 2000; Development (Cambridge, England). 127(5) 957-67. PMID: 10662635
Thisse B, Wright CV, Thisse C, Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo., 2000; Nature. 403(6768) 425-8. PMID: 10667793
Delaunay F, Thisse C, Marchand O, Laudet V, Thisse B, An inherited functional circadian clock in zebrafish embryos., 2000; Science (New York, N.Y.). 289(5477) 297-300. PMID: 10894777
Thisse C, Neel H, Thisse B, Daujat S, Piette J, The Mdm2 gene of zebrafish (Danio rerio): preferential expression during development of neural and muscular tissues, and absence of tumor formation after overexpression of its cDNA during early embryogenesis., 2000; Differentiation; research in biological diversity. 66(2) 61-70. PMID: 11100897
Neyt C, Jagla K, Thisse C, Thisse B, Haines L, Currie PD, Evolutionary origins of vertebrate appendicular muscle., 2000; Nature. 408(6808) 82-6. PMID: 11081511
Fürthauer M, Thisse B, Thisse C, Three different noggin genes antagonize the activity of bone morphogenetic proteins in the zebrafish embryo., 1999; Developmental biology. 214(1) 181-96. PMID: 10491267
Herbomel P, Thisse B, Thisse C, Ontogeny and behaviour of early macrophages in the zebrafish embryo., 1999; Development (Cambridge, England). 126(17) 3735-45. PMID: 10433904
Thisse C, Thisse B, Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction., 1998; Development (Cambridge, England). 126(2) 229-40. PMID: 9847237
Fürthauer M, Thisse C, Thisse B, A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula., 1997; Development (Cambridge, England). 124(21) 4253-64. PMID: 9334274
Taneja R, Thisse B, Rijli FM, Thisse C, Bouillet P, Dollé P, Chambon P, The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos., 1996; Developmental biology. 177(2) 397-412. PMID: 8806819
Thisse B, Thisse C, Weston JA, Novel FGF receptor (Z-FGFR4) is dynamically expressed in mesoderm and neurectoderm during early zebrafish embryogenesis., 1995; Developmental dynamics : an official publication of the American Association of Anatomists. 203(3) 377-91. PMID: 8589434
Thisse C, Thisse B, Postlethwait JH, Expression of snail2, a second member of the zebrafish snail family, in cephalic mesendoderm and presumptive neural crest of wild-type and spadetail mutant embryos., 1995; Developmental biology. 172(1) 86-99. PMID: 7589816
Thisse C, Thisse B, Halpern ME, Postlethwait JH, Goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas., 1994; Developmental biology. 164(2) 420-9. PMID: 8045345
Thisse C, Thisse B, Schilling TF, Postlethwait JH, Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos., 1993; Development (Cambridge, England). 119(4) 1203-15. PMID: 8306883
Thisse C, Thisse B, Dorsoventral development of the Drosophila embryo is controlled by a cascade of transcriptional regulators., 1992; Development (Cambridge, England). Supplement. () 173-81. PMID: 1299363
Thisse C, Perrin-Schmitt F, Stoetzel C, Thisse B, Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product., 1991; Cell. 65(7) 1191-201. PMID: 1648449
Wolf C, Thisse C, Stoetzel C, Thisse B, Gerlinger P, Perrin-Schmitt F, The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes., 1991; Developmental biology. 143(2) 363-73. PMID: 1840517
Thisse B, Stoetzel C, Gorostiza-Thisse C, Perrin-Schmitt F, Sequence of the twist gene and nuclear localization of its protein in endomesodermal cells of early Drosophila embryos., 1988; The EMBO journal. 7(7) 2175-83. PMID: 3416836 | PMCID: PMC454534
Thisse B, el Messal M, Perrin-Schmitt F, The twist gene: isolation of a Drosophila zygotic gene necessary for the establishment of dorsoventral pattern., 1987; Nucleic acids research. 15(8) 3439-53. PMID: 3106932 | PMCID: PMC340740