Transgressions of compartment boundaries and cell reprogramming during regeneration in Drosophila

Abstract

Animals have developed mechanisms to reconstruct lost or damaged tissues. To regenerate those tissues the cells implicated have to undergo developmental reprogramming. The imaginal discs of Drosophila are subdivided into distinct compartments, which derive from different genetic programs. This feature makes them a convenient system to study reprogramming during regeneration. We find that massive damage inflicted to the posterior or the dorsal compartment of the wing disc causes a transient breakdown of compartment boundaries, which are quickly reconstructed. The cells involved in the reconstruction often modify their original identity, visualized by changes in the expression of developmental genes like engrailed or cubitus interruptus. This reprogramming is mediated by up regulation of the JNK pathway and transient debilitation of the epigenetic control mechanism. Our results also show that the local developmental context plays a role in the acquisition of new cell identities: cells expressing engrailed induce engrailed expression in neighbor cells.When cells or tissues are damaged, animals can often regenerate the affected tissues. In an effort to identify the genes and mechanisms that are involved in this regeneration process, researchers often perform experiments on relatively simple organisms or systems. These experiments frequently involve the amputation of specific cells or organs so the researchers can observe and manipulate the events that occur during the subsequent regeneration.One such model organism is the fruit-fly Drosophila. Inside the Drosophila larva are structures called imaginal discs, which are precursors to parts of the outer cuticle of the adult fly. Each imaginal disc contains two main boundaries, dividing it into anterior/posterior and dorsal/ventral compartments: posterior cells, for example, express a gene called engrailed to produce the relevant protein, whereas anterior cells do not; likewise, the gene apterous is expressed in dorsal cells but not ventral cells. These genes, engrailed and apterous, are the key factors that determine the developmental features–and hence the identity—of the posterior and the dorsal cells respectively.Herrera and Morata investigated how cells regenerate when parts of the imaginal disc are destroyed, using a genetic technique that causes high levels of programmed cell death in either the posterior or the dorsal compartments of the disc.Destroying most of the cells in either of these compartments in the imaginal disc leads to a temporary breakdown of the corresponding boundary, which is then rapidly reconstructed. During this reconstruction process, some of the imaginal disc cells are reprogrammed: for example, if the cells in the posterior compartment are destroyed, some anterior cells take on a posterior identity. This reprogramming occurs because the cell destruction disrupts the way that the expression of genes such as engrailed and apterous is controlled by other genes.Neighboring cells can also control gene expression, and therefore cell identity. Cells that express engrailed, for example, cause their neighbors to express engrailed too. This process is likely to involve group interactions that might help the distinct compartments in the imaginal disc to form by ensuring that adjacent cells develop in the same way. Similar processes may also occur as part of the normal development of organisms.