Mechanics and Genetics of Embryonic and Tumoral Development
Group leader : Emmanuel Farge
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)
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).
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)
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).
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).
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).