During Drosophila gastrulation, two waves of constriction occur in the apical ventral cells, leading to mesoderm invagination. The first constriction wave is a stochastic process mediated by the constriction of 40% of randomly positioned mesodermal cells and is controlled by the transcription factor Snail. The second constriction wave immediately follows and involves the other 60% of the mesodermal cells. The second wave is controlled by the transcription factor Twist and requires the secreted protein Fog. Complete mesoderm invagination requires redistribution of the motor protein Myosin II to the apical side of the constricting cells. We show that apical redistribution of Myosin II and mesoderm invagination, both of which are impaired in snail homozygous mutants that are defective in both constriction waves, are rescued by local mechanical deformation of the mesoderm with a micromanipulated needle. Mechanical deformation appears to promote Fog-dependent signaling by inhibiting Fog endocytosis. We propose that the mechanical tissue deformation that occurs during the Snail-dependent stochastic phase is necessary for the Fog-dependent signaling that mediates the second collective constriction wave.

The modulation of developmental biochemical pathways by mechanical cues is an emerging feature of animal development, but its evolutionary origins have not been explored. Here we show that a common mechanosensitive pathway involving β-catenin specifies early mesodermal identity at gastrulation in zebrafish and Drosophila. Mechanical strains developed by zebrafish epiboly and Drosophila mesoderm invagination trigger the phosphorylation of β-catenin–tyrosine-667. This leads to the release of β-catenin into the cytoplasm and nucleus, where it triggers and maintains, respectively, the expression of zebrafish brachyury orthologue notail and of Drosophila Twist, both crucial transcription factors for early mesoderm identity. The role of the β-catenin mechanosensitive pathway in mesoderm identity has been conserved over the large evolutionary distance separating zebrafish and Drosophila. This suggests mesoderm mechanical induction dating back to at least the last bilaterian common ancestor more than 570 million years ago, the period during which mesoderm is thought to have emerged.