Physical chemistry Curie - Institut Curie / CNRS UMR 168 / UPMC

Mechanics and Genetics of Embryonic and Tumoral Development

Group leader: Emmanuel Farge

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Keywords: embryogenesis, tumour development, biomechanics, mechano-transduction, multiscale interplay

Read the scientific activity report. (pdf 438Ko, last update 26th, march 2010)

Embryogenesis involves two main types of morphogenetic process: genetic patterning of the body plan and mechanical movements that create the physical shape of the embryo (movie 1). We know that morphogenetic movements are controlled by expression of patterned developmental genes but, conversely, might the expression of some patterning genes be modulated by mechanical forces in the developing embryo? (Fig. 1)

Fig. 1
Fig. 1 

We are investigating whether the morphogenetic movements of Drosophila embryos influence expression of genes that control their development. We have discovered that, during gastrulation, the process of convergent extension - in which layers of cells intercalate (converge) and become longer (extend) - compresses the future anterior gut cells of the embryo and so induces expression of twist in these cells, which is necessary for proper formation of the anterior gut (Fig. 2).

Fig. 2
Fig. 2 

We have investigated the physiological function of twist mechanical induction in controlling expression of genes that govern anterior gut differentiation in living embryos, as well as the mechano-transduction mechanism involved in this specific case. We also are investigating whether mechanical forces regulate developmental genes in the embryos of other species and whether they regulate homeostatic genes in adult organs.

Specifically, we have observed the mechanical activation of the expression of twist-1 and c-myc genes that initiate the programm of tumoral progression in colon cancer, in genetcially predisposed APC+/-pre-tumoral mice tisues (Fig. 3).

Fig. 3
Fig. 3 

Initially, we used several complementary approaches, including cell biology, which led us to propose a mechanism for mechano-transduction in which membrane tension modulates the endocytosis of signalling proteins, causing strong modulation of downstream gene expression (Fig. 4).

Fig. 4
Fig. 4 

We are working on mechanical signaling in the activation of Myosine-II dependent mesoderm invagination in early Drosophila embryos, and its dependence of Fog endocytosis mechanical inhibition (Fig. 5).

Fig. 5
Fig. 5 

We are now studying other mechanisms by which mechanical cues from gastrulation might activate master genes protein product that control active multi-cellular morphogenetic movements and the formation of primitive organs. Our goal is to investigate if, and how, the macroscopic mechanics of a tissue contribute to the regulation of genes involved at the microscopic level in the morphogenesis of the tissue. In parallel, we develop numerical simulations of the Drosophila embryo gastrulation, to characterize in a quantitative way the biomechanical parameters of morphogenetic movements (Fig. 6 and movie 2).

Fig. 6
Fig. 6 

Movie 1

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Movie 2

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Last update: March 2010

Key publications

2009

  • Pouille PA, Ahmadi P, Brunet AC, Farge E.
    Mechanical signals trigger Myosin II redistribution and mesoderm invagination in Drosophila embryos
    Science Signaling, 14;2(66):ra16 - Full version

2008

  • Desprat N, Supatto W, Pouille PA, Beaurepaire E, Farge E.
    Tissue deformation modulates twist expression to determine anterior midgut differentiation in Drosophila embryos
    Developmental Cell, 15(3):470-7
  • Whitehead J., Vignjevic D., Fütterer C., Beaurepaire E., Robine S. & Farge E.
    Mechanical factors activate beta-catenin-dependent oncogene expression in APC1638N/+ mouse colon
    Human Science Frontiers Programm Journal, 1 October 2008 - Abstract
    Abstract: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2/66/ra16?ijkey=mtztqS.PFzoHQ&keytype=ref&siteid=sigtrans
    Editors summary: http://stke.sciencemag.org/cgi/content/summary/sigtrans;2/66/ra16?ijkey=mtztqS.PFzoHQ&keytype=ref&siteid=sigtrans
    - Full version
  • Pouille, P.A & E. Farge
    Hydrodynamic simulation of multi-cellular embryo lnvagination
    Physical Biology, 5(1):15005
  • Yin, C., Kiskowski, M, Pouille, P.A., Farge, E. and Solnica-Krezel, L.
    Cooperation of polarized cell intercalations drives convergence and extension of presomitic mesoderm during zebrafish gastrulation
    J. Cell Biol, 180(1):221-32

2007

  • Desprat, N. and E. Farge
    In search of the molecular mechano-transducers of the cell
    Medecine Science, 23:583-5

2005

  • Supatto, W., Debarre, D., Moulia, B., Brouzés, E., Martin, J. L., Farge, E. and Beaurepaire, E.
    In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses
    PNAS, 102:1047-1052

2004

  • E. Brouzés, W. Supatto, and E. Farge.
    Is mechano-sensitive expression of twist involved in mesoderm formation?
    Biology of the Cell, 96:471-7
  • Brouzés, E. and Farge, E
    Interplay of Mechanical Deformation and Patterned Gene Expression in Developing Embryos
    Current Opinion in Genetics and Development, 4:367-374

2003

  • E. Farge
    Mechanical Induction of Twist in the Drosophila Fore-Gut/Stomodeal Primordium
    Current Biology, 13:1365-1377

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