Denis Duboule

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Denis Duboule

Denis Duboule (born February 17, 1955 in Geneva ) is a Swiss - French developmental biologist and geneticist at the University of Geneva and the École polytechnique fédérale de Lausanne .

Life

Duboule studied biology at the University of Geneva , where he also obtained a docteur en sciences ( doctor of natural sciences ). As a postdoctoral fellow or group leader, he worked with Pierre Chambon at the University of Strasbourg and then at the European Molecular Biology Laboratory (EMBL) in Heidelberg , before returning to the University of Geneva as a professor in 1992. Since 1997 he has headed the department for zoology and animal biology there. Since 2001 he has headed the national research focus Frontiers in Genetics of the Swiss National Science Foundation .

Duboule is married and has four children.

Act

Duboule carried out fundamental studies on colinearity , a principle according to which the genes that control the development of the limbs in vertebrates (vertebrates) spatially on the one hand along their temporal use during embryonic development , on the other hand along the body axis "front-back" of the species the chromosomes are arranged. He was able to show that the Hox genes play a decisive role in the development of the limbs. His discoveries opened up a new field of research and made a decisive contribution to understanding the evolution of species ( evolutionary developmental biology ).

Denis Duboule's contributions are in the field of genetics of vertebrate development, evolutionary developmental biology, the interface to medical genetics and transcription regulation. Since 1985 he published a series of discoveries about the evolutionary development of the vertebrate body, in particular the family of the Hox genes, 1986 on the cloning and structure of the first large Hox gene complex of the mouse and in collaboration with G. Gaunt on the expression of a Hox Gene in neuromas in the rhombencephalon , suggesting an analogy for the expression of related genes in the fruit fly (Drosophila). In 1988, together with G. Gaunt, he wrote about the colinear expression of Hox genes in vertebrates and thus decisively expanded the existence of this phenomenon from Drosophila to vertebrates and other new mouths. In 1989 he described temporal colinearity (the Hox clock), an extension of the same principle of colinearity to the timing of the transcriptional activation of these genes. In 1989, together with the Krumlauf laboratory, the discovery of the structural conservation of the entire homeotic system in mice and flies followed; thereafter there is a single homeotic complex in the animal family tree of the primordial mouths and new mouths . In 1989 and 1991 it was first reported that the same genetic system was used multiple times in the organization of structures along different axes, especially in vertebrate extremity and in the genitourinary system. The extension of this work to birds together with Cheryll Tickle and Lewis Wolpert demonstrated both the high degree of inter-species conservation and the essential role of these genes in limb development . In 1991 Duboule published his "Concept of Posterior Prevalence". It stands for the functional organization of the Hox genes. In 1993 he showed that Hox genes are involved in multiple axial structures. This happens via a mutation of a single Hox gene, which leads to massive changes in the extremities, the axial skeleton and the external genital organs.

In 1994 he proposed the concept of the "developmental hourglass". In doing so, he called for a restriction of the phenotypic landscapes in a certain phase of vertebrate development, on the basis of maximum mechanistic constraints . The suggestion that Hox genes act as a “clock” and that all vertebrates develop their body axis in a time sequence requires at least one complete Hox cluster in order to be able to integrate the time parameter. In 1995, the description of Hox genes in zebrafish and their expression during fin development followed. This led to a possible scheme of the evolutionary transition from the fin to the extremity, in which fingers or toes are seen as an innovation that occurred along with the appearance of the tetrapods . In 1996, a relationship between the dominant negative function of Hox genes and a human genetic syndrome (type II syndactyly or polysyndactyly ) was established via posterior prevalence.

From 1997 to 2001, Duboule's laboratory investigated the problem of colinearity on a mechanistic level using embryonic stem cell-based genetics; Hox genes are controlled on a general level, which involves their respective position in the gene cluster. In 2001 a connection was established between temporal colinerarity (Hoxuhr) and the thusic clock, according to which the progression and specification of the somites are coordinated. “ Now that we had understood which genes control the limbs of all vertebrates, we were interested in what happens when these genes are exchanged in order to better understand how our organism works. ” From 1998 this laboratory therefore used two of its own genetic approaches , TAMERE (targeted meiotic recombination) and STRING to start a large-scale in vivo gene regulation analysis. This led to concepts of “regulatory landscapes” or “archipelagos”. This large series of alleles recently made it possible to discover the mechanism underlying colinearity in the development of vertebrate extremity. In fact, the axial organization of our legs and arms corresponds to the linear organization of regulatory chromatin domains. The transition between these chromosomal domains corresponds to the wrist, that is, the transition between the old (arms and legs) and the new part (hands and feet) of our limbs. Duboule also studied in detail the biochemical mechanisms that govern the Hox gene regulation and the process of the Hox clock during the formation of the main body axis. This clock is connected to a transition into chromatin domains, which is accompanied by a step-by-step gene change from a negative to a positive chromatin compartment.

The potential importance of these observations for our understanding of gene regulation in development and morphological evolution has been discussed in various reviews.

Awards (selection)

Membership in the advisory board or editorial committee of science magazines

  • Editor Development (1995-2005)
  • Editor Developmental Biology (2014-)
  • Board of Reviewing Editors Science (2002–2010)
  • Associate Editor EMBO Journal (1994-1996, 1999-2001).
  • Associate Editor Mechanism of Development (-2010)
  • Associate Editor Gene Expression Patterns (-2010)
  • Associate Editor Developmental Biology .
  • Associate Editor Genes to Cells .
  • Associate Editor International Journal of Dev. Biology .
  • Associate Editor International Journal of Molecular Medicine .
  • Associate Editor Evolution and Development . (1999-2005)
  • Associate Editor Médecine / Sciences
  • Associate Editor EMBO Reports (1999–2001)
  • Associate Editor BioEssays (2005-)
  • Advisory board Genome Biology

Publications

items

Books

  • as publisher: A guidebook to homeobox genes. Oxford University Press, 1994.
  • with E. Hafen and D. Bopp (eds.): Developmental Biology in Switzerland. (= International journal of developmental biology. Volume 46). UBC Press, 2002.

Interviews

Web links

Commons : Denis Duboule  - collection of images, videos and audio files

Individual evidence

  1. ↑ D. Duboule, A. Baron, P. Mahl, B. Galliot, A new homeo-box is present in overlapping cosmid clones which define the mouse Hox-1 locus. Embo J 5, 1973 (Aug, 1986).
  2. ↑ SJ Gaunt, JR Miller, DJ Powell, D. Duboule, Homoeobox gene expression in mouse embryos varies with position by the primitive streak stage. Nature 324, 662 (Dec 18-31, 1986).
  3. ↑ SJ Gaunt, PT Sharpe, D. Duboule, Spatially restricted domains of home gene transcripts in mouse embryos: relation to a segmented body plan. Development, 104: 169 (1988).
  4. ↑ JC Izpisua-Belmonte, H. Falkenstein, P. Dolle, A. Renucci, D. Duboule, Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. Embo J 10, 2279 (Aug, 1991).
  5. ↑ a b P. Dolle, JC Izpisua-Belmonte, H. Falkenstein, A. Renucci, D. Duboule, Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation. Nature 342, 767 (Dec 14, 1989).
  6. ↑ D. Duboule, P. Dolle, The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. Embo J 8, 1497 (May, 1989).
  7. ↑ P. Dolle, JC Izpisua-Belmonte, JM Brown, C. Tickle, D. Duboule, HOX-4 genes and the morphogenesis of mammalian genitalia. Genes Dev 5, 1767 (Oct, 1991).
  8. ↑ JC Izpisua-Belmonte, C. Tickle, P. Dolle, L. Wolpert, D. Duboule, Expression of the homeobox Hox-4 genes and the specification of position in chick wing development. Nature 350,585 (Apr 18, 1991).
  9. ↑ a b c D. Duboule, Temporal colinearity and the phylotypic progression: a basis for the stability of a vertebrate building plan and the evolution of morphologies through heterochrony. Dev Suppl, 135 (1994).
  10. ↑ a b D. Duboule, The vertebrate limb: a model system to study the Hox / HOM gene network during development and evolution. Bioessays 14, 375 (Jun, 1992).
  11. ↑ P. Dolle et al., Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs. Cell 75, 431 (Nov 5, 1993).
  12. ↑ P. Sordino, F. van der Hoeven, D. Duboule, Hox gene expression in teleost fins and the origin of vertebrate digits. Nature 375, 678 (Jun 22, 1995).
  13. ^ J. Zákány, D. Duboule, Synpolydactyly in mice with a targeted deficiency in the HoxD complex. Nature 384, 69 (Nov 7, 1996).
  14. ^ F. van der Hoeven, J. Zákány, D. Duboule, Gene transpositions in the HoxD complex reveal a hierarchy of regulatory controls. Cell 85,1025 (Jun 28, 1996).
  15. ↑ M. Kmita, N. Fraudeau, Y. Herault, D. Duboule, Serial deletions and duplications suggest a mechanism for the collinearity of Hoxd genes in limbs. Nature 420, 145 (Nov 14, 2002).
  16. ^ T. Kondo, D. Duboule, Breaking colinearity in the mouse HoxD complex. Cell 97, 407 (Apr 30, 1999).
  17. ↑ J. Zakany, M. Kmita, P. Alarcon, JL de la Pompa, D. Duboule, Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock. Cell 106, 207 (Jul 27, 2001).
  18. ↑ Prof. Dr. Denis Duboule, Institute for Genetics & Evolution, University of Geneva & Swiss Institute for Experimental Cancer Research, EPFL - GEN SUISS. In: gensuisse.ch. Retrieved April 6, 2018 .
  19. ^ F. Spitz, F. Gonzalez, D. Duboule, A global control region defines a chromosomal regulatory landscape containing the HoxD cluster. Cell 113, 405 (May 2, 2003).
  20. ↑ a b T. Montavon et al., A regulatory archipelago controls Hox genes transcription in digits. Cell 147, 1132 (Nov 23, 2011).
  21. ↑ B. Tarchini, D. Duboule, Control of Hoxd genes' collinearity during early limb development. Dev Cell 10, 93 (Jan, 2006).
  22. ↑ a b G. Andrey et al., A switch between topological domains underlies HoxD genes collinearity in mouse limbs. Science 340, 1234167 (Jun 7, 2013).
  23. ↑ N. Soshnikova, D. Duboule, Epigenetic temporal control of mouse Hox genes in vivo. Science 324, 1320 (Jun 5, 2009).
  24. ↑ D. Noordermeer et al., The dynamic architecture of Hox gene clusters. Science 334, 222 (Oct 14, 2011).
  25. ^ D. Duboule, The rise and fall of Hox gene clusters. Development 134, 2549 (Jul, 2007).
  26. ↑ W. de Laat, D. Duboule, Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502, 499 (Oct 24, 2013).
  27. ↑ M. Kmita, D. Duboule, Organizing axes in time and space; 25 years of colinear tinkering. Science 301,331 (Jul 18, 2003).
  28. ^ National Latsis Prize. (No longer available online.) In: snf.ch. Archived from the original on February 9, 2016 ; accessed on February 9, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.snf.ch
  29. ^ Denis Duboule at the Academia Europaea (ae-info.org); Retrieved August 6, 2011.
  30. ↑ Les lauréats du Prix Louis-Jeantet de médecine 1998 ( Memento of the original dated August 30, 2011 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. at the Louis Jeantet Foundation (jeantet.ch); Retrieved August 4, 2011. @1@ 2Template: Webachiv / IABot / www.jeantet.ch
  31. ↑ Duboule, Prof. dr. D. (Denis) - KNAW. In: knaw.nl. Retrieved February 11, 2016 .
  32. ↑ Denis Duboule at the Marcel Benoist Foundation (marcel-benoist.ch); Retrieved August 4, 2011.
  33. ^ Prix ​​Charles-Léopold Mayer. List of award winners (PDF, 1.8 MB, status 2014) at academie-sciences.fr; accessed on February 1, 2016.
  34. ↑ Denis Duboule and curriculum vitae (PDF, 30 kB) at the Académie des sciences (academie-sciences.fr); accessed on February 10, 2016.
  35. ↑ Book of Members 1780 – present, Chapter D. (PDF; 575 kB) In: American Academy of Arts and Sciences (amacad.org). Accessed April 6, 2018 .
  36. ↑ Denis Duboule, Prix International 2010. In: histoire.inserm.fr. Retrieved April 6, 2018 (French).
  37. ^ Foreign Members of the Royal Society (royalsociety.org); Retrieved September 24, 2012.
personal data
SURNAME Duboule, Denis
BRIEF DESCRIPTION Franco-Swiss developmental biologist and geneticist
DATE OF BIRTH 17th February 1955
PLACE OF BIRTH Geneva