Date : 23/4/2010

Laboratory

Mechanics and Genetics of Embryonic development
UMR 168, Physico-Chimie Curie
11 rue Pierre et Marie Curie 75005 Paris
Director : Jean-François Joanny

PhD Supervisor

Emmanuel Farge
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 156246760

Subjects / Tools-Methodologies

1 : Myosin-II/Myo-GFP transgenic flies
2 : Mechanical strains/Ferro-fluid magnets
3 : Modeling/Analytical and simulations

Summary of lab's interests

The thematic of the group focuses on the role of mechanical strain and deformation of macroscopic biological structures at the cell or multi-cellular level, into the regulation and the generation of active physiological processes at the microscopic molecular cell level, including gene expression. Historically, the first main thematic studied was the motor role of biological membrane elasticity into the budding driving force of vesiculation initiating plasma membrane endocytosis.Today, these thematic are: 1- regulation of patterning gene expression of embryonic development by mechanical strains developed by morphogenetic movements / 2- regulation of tumour development gene expression by mechanical strains developed by tumour growth onto the stroma.

Summary of project

Mesoderm invagination is one of the major morphogenetic movement of gastrulation. In the Drosophila embryo, it is triggered by the constriction of the apexes of mesoderm cells, therefore taking the mean conical shape leading to the invagination of the mesoderm tissue inside the embryo. A first constriction phase, slow and stochastic, involves 40% of mesoderm cells under the control of the sna gene, directly followed by the collective constriction of the other 60% of cells. This second phase is controlled by a process of apical stabilisation of Myosin-II (Myo-II) depending on Fog expression, which generates mesoderm invagination. Fog is a secreted factor expressed into the mesoderm with Snail. We have proposed that the interaction between the two pathways is mechanical in nature, the Snail dependent stochastic phase triggering the mechanical strains that activate the Fog signalling pathway. Our published data effectivelyshow that mechanically indenting the mesoderm rescues apical stabilisation and invagination of the mesoderm missing in Snail mutants.

THE OBJECTIVE OF THE PROJECT IS TO MODEL AND TEST EXPERIMENTALLY THE EXISTENCE OF A TRANSITION OF COORDINATED COLLECTIVE CONSTRICTIONS INDUCED BY A PROCESS OF STOCHASTIC INDIVIDUAL CONSTRICTIONS VIA THE MECHANO-SENSITIVITY OF THE FOG SIGNALLING PATHWAY.

The originality of the problematics is the high definition of the molecular to multi-cellular coupling process, due to 25 years of genetics in the field. As well as the fact that due to mechano-transduction, we here have an atypical system in which fluctuations lead to organisation, in opposition to classical statistical physics systems. References: 1. Farge, E. (2003) Curr Biol 13, 1365-77. 2. Brouzes, E., and Farge, E. (2004) Curr Opin Genet Dev 14, 367-74. 3. Desprat, N., Supatto, W., Pouille, P. A., Beaurepaire, E., and Farge, E. (2008) Dev Cell 15, 470-7. 4. Pouille, P. A., Ahmadi, P., Brunet, A. C., and Farge, E. (2009) Sci Signal 2, ra16. 5. Pouille, P. A., and Farge, E. (2008) Phys Biol 5, 15005.