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From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction

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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 beta-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 beta-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence1.We additionally find mechanical activation of beta-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure in vivo 2-4.

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