Group of Mechanics and Genetics of Embryonic Development, CNRS UMR168 / Institut Curie, Paris.

will give a seminar on Thursday the 12th of January, 2017
at 11 AM in amphitheater Curie (How appropriate !)

Mechanosensitivity of junctional beta-catenin : 

from mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction

Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue
from which most of animal complex organs develop. Mesoderm emerged 570 millions years
ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack
of conservation of biochemical signalling proteins upstream of early embryonic mesoderm
differentiation across bilaterians prevents to answer the question of the signal having been at
the origin evolutionary origin of mesoderm emergence and complex animals. Here we found
the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first
morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and
nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate
zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last
common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as
having initiated the evolutionary transition to mesoderm differentiation and complex animals
evolutionary emergence¹.
We additionally find mechanical activation of β-catenin as involved in the mechanical
activation of tumorigenic biochemical pathways, in the healthy epithelium compressed by the
neighbouring tumour, in response to tumour growth pressure in vivo^2-4.

1 Brunet, T., [...], Farge, E. Evolutionary conservation of early mesoderm specification by
mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).
2 Whitehead, J., [...], Farge, E. Mechanical factors activate beta-catenin-dependent oncogene
expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).
3 Fernandez-Sanchez, M. E., Barbier, S., [...], Farge, E. Mechanical induction of the tumorogenic β-
catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in
Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-
cellbio-102314-112441 (2015).
Websites :
http://cvscience.aviesan.fr/cv/818/emmanuel-farge
http://umr168.curie.fr/en/Farge-group

Date : 12/01/2017 à 11h

Lieu : Amphi Curie

Contact : Nous contacter