During development, cells become determined or fixed in particular developmental pathways. However, each primordium contains a few cells that can be stimulated to change their fate. For example, in Drosophila,ectopic Wingless expression induces specific leg imaginal disc cells to transdetermine into wing cells. Klebes and co-workers investigate how this example of cellular plasticity is regulated by examining gene expression patterns in transdetermining cells and non-transdetermining cells from the same disc (see p. 3753). Genes implicated in transdetermination by this analysis include lamina ancestor (lama) and the Polycomb and trithorax group of chromatin regulators; functional assays provide additional evidence for the involvement of these genes in transdetermination. The researchers conclude that transdetermination depends on resetting the chromatin structure, which is only possible in a few cells. These insights into developmental plasticity may advance the development of human stem cells for medical applications.