Epithelial–mesenchymal transitions: A mesodermal cell strategy for evolutive innovation in Metazoans

Epithelial-mesenchymal transitions (EMTs) are well known processes in which new mesenchyme is locally generated from epithelia. During the development of the vertebrate embryo, EMTs are a source of mesenchyme in diverse places and stages through embryonic morphogenesis, especially in mesodermal domains. In the present work we consider the embryo as a two-state system in which epithelium and mesenchyme represent the stable and unstable states, respectively. We think that a pattern of recurrent oscillations between the plasticity and exploratory behaviour of the mesenchyme and the stability of the epithelia can be recognized in the embryogenesis of vertebrates and, probably, in most tripoblastic Metazoans. Mesoderm, in particular, might be regarded as a cell layer able to oscillate between epithelial and mesenchymal states. The cellular and molecular mechanisms that enable these recurrent oscillations between stable (epithelial) and unstable (mesenchymal) states during embryogenesis provide the mesoderm with a large plasticity, an extended potential for innovation, and a better control of the three-dimensional (3D) body organization. In this scenario, it is conceivable that the origin of the mesoderm itself might be related to ancestral mechanisms regulating cell adhesion and detachment. We conclude that EMTs played a key role in the evolution of Metazoans, and are involved in the pathological and reparative processes of adult organisms.