Mechanical forces drive embryonic development
Our knowledge on embryonic development mainly comes from studies on cell signalling in response to chemical cues. However, our understanding of the molecular mechanism by which cells receive and transduce mechanical signals into biochemical signals is poor. With this in mind, scientists on the EU-funded BCATENIN_MECHANICS (Mechanical activation of beta-catenin signalling) study set out to provide in vivo insight into this largely unexplored mechanism. For this purpose, they chose to study the beta-catenin pathway, which is involved in the mechanical induction of mesoderm differentiation at gastrulation. The consortium was interested to understand the mechanical activation process. Using Drosophila as a model organism and state-of-the-art live imaging techniques, scientists discovered that the strain generated during drosophila gastrulation weakens the interaction of beta-catenin with other proteins. In addition, the protein becomes more amenable to phosphorylation, a modification that further inhibits beta-catenin intermolecular interaction. These observations clearly indicate that during development beta-catenin serves as the primary sensor of mechanical forces. Comparison of the beta-catenin molecular sequence across different species indicated that this mechanosensitive site is conserved. In mice, activation of the beta-catenin pathway in response to mechanical strain is observed in bone mass formation and homeostasis, as well as in adipogenesis. The future plans of the consortium include the design of a fluorescent probe to directly monitor mechanical activation in response to morphogenetic movements during Drosophila gastrulation. The findings of the study could also aid cancer research as mechanical activation of beta-catenin by tumour cells in healthy tissues is carcinogenic.
Keywords
Mechanical force, embryonic development, beta-catenin, Drosophila, cancer research
