Bernard V. Thisse


  • PhD, University of Strasbourg
  • Postdoc, IGBMC_CNRS
  • Postdoc, University of Oregon

Primary Appointment

  • Professor, Cell Biology


Research Interest(s)

Molecular control of embryonic development

Research Description

From the fertilized egg to the fully differentiated organism, cells undergo proliferation, differentiation and morphogenesis. These different functions are controlled by sets of instructing signaling that have been conserved across evolution and that turn ON, OFF or that regulate the developmental programs required to form the different tissues and organs of a mature individual. During early embryonic development a handful of signaling pathways, activated by a small number of secreted factors acting as morphogens, are sufficient to pattern the growing embryos along antero-posterior and dorso-ventral axes and to induce a bilateral asymmetry defining a left and a right side. 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. Seminars in cell & developmental biology. 2015. PMID: 25999320
  • Lu F, Sun Y, Wei C, Thisse C, Thisse B. Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway. Nature communications. 2014;5 5368. PMID: 25371059
  • Xu P, Houssin N, Ferri-Lagneau K, Thisse B, Thisse C. Construction of a vertebrate embryo from two opposing morphogen gradients. Science (New York, N.Y.). 2014;344(6179): 87-9. PMID: 24700857
  • Lu F, Thisse C, Thisse B. Identification and mechanism of regulation of the zebrafish dorsal determinant. Proceedings of the National Academy of Sciences of the United States of America. 2011;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. Developmental biology. 2010;350(2): 484-95. PMID: 21172337
  • Fauny J, Thisse B, Thisse C. The entire zebrafish blastula-gastrula margin acts as an organizer dependent on the ratio of Nodal to BMP activity. Development (Cambridge, England). 2009;136(22): 3811-9. PMID: 19855023
  • Thisse C, Thisse B. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nature protocols. 2008;3(1): 59-69. PMID: 18193022
  • Bertrand S, Thisse B, Tavares R, Sachs L, Chaumot A, Bardet P, 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. PLoS genetics. 2007;3(11): e188. PMID: 17997606 | PMCID: PMC2065881
  • Huang H, Lu F, 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. Development (Cambridge, England). 2007;134(5): 979-88. PMID: 17293535
  • Dal-Pra S, Fürthauer M, Van-Celst J, Thisse B, Thisse C. Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP activity. Developmental biology. 2006;298(2): 514-26. PMID: 16890217
  • 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. Experimental cell research. 2006;313(1): 156-67. PMID: 17123513
  • Poulain M, Fürthauer M, Thisse B, Thisse C, Lepage T. Zebrafish endoderm formation is regulated by combinatorial Nodal, FGF and BMP signalling. Development (Cambridge, England). 2006;133(11): 2189-200. PMID: 16672336
  • Seiliez I, Thisse B, Thisse C. FoxA3 and goosecoid promote anterior neural fate through inhibition of Wnt8a activity before the onset of gastrulation. Developmental biology. 2005;290(1): 152-63. PMID: 16364286
  • Thisse B, Thisse C. Functions and regulations of fibroblast growth factor signaling during embryonic development. Developmental biology. 2005;287(2): 390-402. PMID: 16216232
  • Fürthauer M, Van Celst J, Thisse C, Thisse B. Fgf signalling controls the dorsoventral patterning of the zebrafish embryo. Development (Cambridge, England). 2004;131(12): 2853-64. PMID: 15151985
  • Thisse B, Heyer V, Lux A, Alunni V, Degrave A, Seiliez I, Kirchner J, Parkhill J, Thisse C. Spatial and temporal expression of the zebrafish genome by large-scale in situ hybridization screening. Methods in cell biology. 2004;77 505-19. PMID: 15602929
  • Agathon A, Thisse C, Thisse B. The molecular nature of the zebrafish tail organizer. Nature. 2003;424(6947): 448-52. PMID: 12879074
  • Delaunay F, Thisse C, Thisse B, Laudet V. Differential regulation of Period 2 and Period 3 expression during development of the zebrafish circadian clock. Gene expression patterns : GEP. 2003;3(3): 319-24. PMID: 12799078
  • 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. Current biology : CB. 2003;13(16): 1429-34. PMID: 12932328
  • Fürthauer M, Lin W, Ang S, Thisse B, Thisse C. Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling. Nature cell biology. 2002;4(2): 170-4. PMID: 11802165
  • 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. Developmental biology. 2002;238(2): 274-88. PMID: 11784010
  • 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. Development (Cambridge, England). 2002;129(1): 25-36. PMID: 11782398
  • Agathon A, Thisse B, Thisse C. Morpholino knock-down of antivin1 and antivin2 upregulates nodal signaling. Genesis (New York, N.Y. : 2000). 2001;30(3): 178-82. PMID: 11477702
  • Fürthauer M, Reifers F, Brand M, Thisse B, Thisse C. sprouty4 acts in vivo as a feedback-induced antagonist of FGF signaling in zebrafish. Development (Cambridge, England). 2001;128(12): 2175-86. PMID: 11493538
  • Kikuchi Y, Agathon A, Alexander J, Thisse C, Waldron S, Yelon D, Thisse B, Stainier D. casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish. Genes & development. 2001;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. Genes & development. 2001;15(21): 2877-85. PMID: 11691838 | PMCID: PMC312811
  • Delaunay F, Thisse C, Marchand O, Laudet V, Thisse B. An inherited functional circadian clock in zebrafish embryos. Science (New York, N.Y.). 2000;289(5477): 297-300. PMID: 10894777
  • Neyt C, Jagla K, Thisse C, Thisse B, Haines L, Currie P. Evolutionary origins of vertebrate appendicular muscle. Nature. 2000;408(6808): 82-6. PMID: 11081511
  • Schmid B, Fürthauer M, Connors S, Trout J, Thisse B, Thisse C, Mullins M. Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development (Cambridge, England). 2000;127(5): 957-67. PMID: 10662635
  • Thisse B, Wright C, Thisse C. Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo. Nature. 2000;403(6768): 425-8. PMID: 10667793
  • 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. Differentiation; research in biological diversity. 2000;66(2): 61-70. PMID: 11100897
  • Fürthauer M, Thisse B, Thisse C. Three different noggin genes antagonize the activity of bone morphogenetic proteins in the zebrafish embryo. Developmental biology. 1999;214(1): 181-96. PMID: 10491267
  • Herbomel P, Thisse B, Thisse C. Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development (Cambridge, England). 1999;126(17): 3735-45. PMID: 10433904
  • Thisse C, Thisse B. Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction. Development (Cambridge, England). 1998;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. Development (Cambridge, England). 1997;124(21): 4253-64. PMID: 9334274
  • Taneja R, Thisse B, Rijli F, 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. Developmental biology. 1996;177(2): 397-412. PMID: 8806819
  • Thisse B, Thisse C, Weston J. Novel FGF receptor (Z-FGFR4) is dynamically expressed in mesoderm and neurectoderm during early zebrafish embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists. 1995;203(3): 377-91. PMID: 8589434
  • Thisse C, Thisse B, Postlethwait J. 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. Developmental biology. 1995;172(1): 86-99. PMID: 7589816
  • Thisse C, Thisse B, Halpern M, Postlethwait J. Goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas. Developmental biology. 1994;164(2): 420-9. PMID: 8045345
  • Thisse C, Thisse B, Schilling T, Postlethwait J. Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos. Development (Cambridge, England). 1993;119(4): 1203-15. PMID: 8306883
  • Thisse C, Thisse B. Dorsoventral development of the Drosophila embryo is controlled by a cascade of transcriptional regulators. Development (Cambridge, England). Supplement. 1992; 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. Cell. 1991;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. Developmental biology. 1991;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. The EMBO journal. 1988;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. Nucleic acids research. 1987;15(8): 3439-53. PMID: 3106932 | PMCID: PMC340740