Mol Syst Biol. 1: 2005.0031 A long‐standing problem in developmental biology, closely associated with pattern formation, is how continuous morphogen gradients are translated into sharp response borders that define clearcut territories in which cells express different sets of genes. To understand how gradients can generate thresholds, several mechanisms have been investigated over the years. Initially, most of these studies were of a theoretical nature, unrelated to any specific example based on solid molecular background. In an elegant study currently published in Molecular Systems Biology (Melen et al , 2005), blending experiment with theory, Shilo, Barkai and co‐workers address this question within the context of a well‐selected developmental system. They resort to computational systems biology to uncover the role of a phosphorylation–dephosphorylation cycle in generating a sharp boundary separating distinct developmental domains in the Drosophila embryo. The phenomenon considered underlies pattern formation in the Drosophila embryonic ventral ectoderm. There, a graded MAPK activation results from a graded activation of the EGF receptor, via the binding of its ligand Spitz secreted by a single row of cells positioned along the midline of the ventral ectoderm. Degradation of the transcriptional repressor Yan is triggered upon phosphorylation by MAPK. Melen et al show that the boundaries of Yan degradation on the two sides of the midline are extremely sharp. The Yan protein is absent from 1–2 cell rows on each side of the midline, whereas the adjacent rows display high levels of Yan comparable to those seen in most lateral cells (Figure 1). How the graded MAPK activation is converted into an all‐or‐none degradation switch of Yan is the topic of this study. Figure 1. (Top) Schematic representation of MAPK activity and total Yan level as a function of distance from midline of ventral ectoderm in the …