A Model of Somitogenesis

Abstract

A quantitative description of the molecular networks that sustain morphogenesis is one of the main challenges of developmental biology. In particular, a molecular understanding of the segmentation of the antero-posterior axis in vertebrates has yet to be achieved. This process known as somitogenesis is believed to result from the interactions between a well-studied genetic oscillator and a less established posterior-moving determination wavefront. Here we describe a molecular model for somitogenesis that couples a moving morphogen wavefront with the somitogenetic oscillator. The wavefront is due to a switch between stable states that results from reciprocal negative feedbacks of Retinoic Acid (RA) on the activation of a kinase ErK and of ErK on RA synthesis. We suggest a molecular mechanism by which that switch can be triggered by the somitogenetic clock. The model quantitatively accounts for the shortening of the pre-somitic mesoderm (PSM) in zebrafish in response to the decrease during somitogenesis in the concentration of a morphogen (Fgf8). The generality and robustness of the model allows for its validation (or invalidation) in other model organisms.