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 been involved in the evolutionary transition to mesoderm differentiation and complex animals emergence1.

We additionally found 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. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).
2  Whitehead, J. et al. 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. & al., 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).