Christine I. Thisse

Education

  • PhD, Louis Pasteur University of Strasbourg
  • Postdoc, University of Oregon

Primary Appointment

  • Professor, Cell Biology

Contact

Research Interest(s)

Molecular Mechanisms of Early Vertebrate Development and Morphogenesis. Application to Stem Cell Biology and Regenerative Medicine

Research Description

Morphogenesis concerns the fundamental question of the biological form, including the study of how cellular differentiation and cell growth occur, leading to the formation of stereotypical and well shaped tissues and organs. Our lab investigates how a vertebrate embryo is patterned and gets its shape during early stages of embryogenesis. We use 2 model systems: the early zebrafish embryo and embryoid bodies made of mouse embryonic stem cells. During the past two decades, we have achieved an extensive analysis of the factors responsible for establishing the dorso-ventral and antero-posterior axes of the zebrafish embryo, focusing on the role of BMP, FGFs and their respective inhibitors (Furthauer et al, 2001; Furthauer et al, 2002; Furthauer et al, 2004) and of Nodal, Activin and their antagonist Antivin/Lefty (Thisse and Thisse, 1999; Thisse et al, 2000; Agathon et al, 2003). We identified also the maternally provided Wnt8a as the factor responsible for the first symmetry-breaking event in the embryo and defined how its activity is regulated by specific antagonists (Lu et al 2011). Part of the lab is now studying how Left-Right asymmetry is setup and controlled. We recently discovered an unsuspected role for factors mediating or regulating the transcriptional response to the Hippo pathway (known as a major regulator of tissue growth and organ size through the regulation of cell proliferation and apoptosis) in the formation of the ciliated organ responsible for the Left-Right asymmetry of the embryo: the Left-right organizer. Using Talen and Crispr/Cas9 editing technologies as well as various gain of function and gene knockdown methods, we are currently dissecting the molecular mechanisms regulating the formation of the Left-Right organizer. In addition, through a comprehensive analysis of the transcriptome of its precursor cells in various loss of function conditions, we will characterize the cascade of gene products involved in its formation and function.

Development of vertebrate embryos involves tightly regulated molecular and cellular processes that progressively instruct proliferating embryonic cells about their identity and behavior. Looking for the minimal conditions and factors that are sufficient to instruct pluripotent cells to organize the embryo, we found that as little as two opposing gradients of morphogens, BMP and Nodal, are sufficient to induce molecular and cellular mechanisms required to organize uncommitted cells of the zebrafish blastula into a well-developed embryo. Applying this combination of two gradients is also sufficient to instruct pluripotent zebrafish blastula cells to organize, in vitro, embryoids containing a full range of tissues and organs (Fauny et al, 2009; Xu et al, 2014; Thisse and Thisse, 2015). Because the signaling pathways controlling the early embryonic development have been conserved across evolution, we predict that these findings can apply to the organization of early mammalian embryos. Therefore, we are now trying to take control of aggregates of mouse embryonic stem cells (embryoid bodies), instructing them through experimentally engineered morphogen gradients that should allow us to control cell fate and morphogenesis. Our goal is to use this approach to induce the formation of tissues and organs in vitro. We predict that this study will have a significant impact on Stem Cell Biology research and will move the field of Regenerative Medicine closer to the goal of achieving the production in vitro of functional organs that could be efficient substitutes for donor organ transplantation in the future. Finally, induction of morphogenesis with symmetry breaking signaling will provide a general framework that may be extended to the organization of other three-dimensional biological systems.

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
  • 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
  • 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
  • Gamse J, Kuan Y, Macurak M, Brösamle C, Thisse B, Thisse C, Halpern M. Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target. Development (Cambridge, England). 2005;132(21): 4869-81. PMID: 16207761
  • 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
  • Galloway J, Wingert R, Thisse C, Thisse B, Zon L. Loss of gata1 but not gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos. Developmental cell. 2004;8(1): 109-16. PMID: 15621534
  • Agathon A, Thisse C, Thisse B. The molecular nature of the zebrafish tail organizer. Nature. 2003;424(6947): 448-52. PMID: 12879074
  • Gamse J, Thisse C, Thisse B, Halpern M. The parapineal mediates left-right asymmetry in the zebrafish diencephalon. Development (Cambridge, England). 2003;130(6): 1059-68. PMID: 12571098
  • Ciruna B, Weidinger G, Knaut H, Thisse B, Thisse C, Raz E, Schier A. Production of maternal-zygotic mutant zebrafish by germ-line replacement. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(23): 14919-24. PMID: 12397179 | PMCID: PMC137520
  • David N, Sapède D, Saint-Etienne L, Thisse C, Thisse B, Dambly-Chaudière C, Rosa F, Ghysen A. Molecular basis of cell migration in the fish lateral line: role of the chemokine receptor CXCR4 and of its ligand, SDF1. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(25): 16297-302. PMID: 12444253 | PMCID: PMC138605
  • 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
  • Thisse C, Zon L. Organogenesis--heart and blood formation from the zebrafish point of view. Science (New York, N.Y.). 2002;295(5554): 457-62. PMID: 11799232
  • 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
  • Gamse J, Shen Y, Thisse C, Thisse B, Raymond P, Halpern M, Liang J. Otx5 regulates genes that show circadian expression in the zebrafish pineal complex. Nature genetics. 2001;30(1): 117-21. PMID: 11753388
  • 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
  • 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
  • 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
  • Miller-Bertoglio V, Carmany-Rampey A, Fürthauer M, Gonzalez E, Thisse C, Thisse B, Halpern M, Solnica-Krezel L. Maternal and zygotic activity of the zebrafish ogon locus antagonizes BMP signaling. Developmental biology. 1999;214(1): 72-86. PMID: 10491258
  • 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
  • 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