Developmental potential for morphogenesis in vivo and in vitro

Abstract

Development is a complex process that involves differentiation into a variety of cell types. In spite of its complexity, the macroscopic pattern and cell types are robust to environmental and developmental perturbations. Even in vitro far from normal developmental conditions, ten normal tissues have been generated from Xenopus animal caps by successive treatment with activin and retinoic acid (RA). To describe both normal development and in vitro organogenesis, we introduce developmental potential following the pioneering study by Waddington. This potential value represents changeability of a cellular state, which decreases toward a local minimum through development. The attraction to a particular cell type through development is described as a process to decrease the potential value to its local minimum. By choosing an explicit potential form as a function of the concentrations of treated activin and RA, the concentration dependence of in vitro organogenesis is reproduced. The potential landscape is shown to have several local minima, each of which represents a stable cell type. This potential also explains why the induction of given tissues requires more treatment of activin at later stages. The consequences of the developmental potential hypothesis encompass the robustness of each tissue generation, the loss of competence through development, and the order of tissues in induction by tissues, which we have confirmed experimentally for in vitro organogenesis. The developmental potential hypothesis for a global description of early development is crucial to understanding the robustness of morphogenesis and explains the achievement of in vitro organogenesis using few molecules as well.