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The activation of MAPKs is controlled by the balance between MAPK kinase and MAPK phosphatase activities. The latter is mediated by a subset of phosphatases with dual specificity (VH-1 family). Here, we describe a new member of this family encoded by the puckered gene of Drosophila. Mutations in this gene lead to cytoskeletal defects that result in a failure in dorsal closure related to those associated with mutations in basket, the Drosophila JNK homolog. We show that puckered mutations result in the hyperactivation of DJNK, and that overexpression of puc mimics basket mutant phenotypes. We also show that puckered expression is itself a consequence of the activity of the JNK pathway and that during dorsal closure, JNK signaling has a dual role: to activate an effector, encoded by decapentaplegic, and an element of negative feedback regulation encoded by puckered. In many cases, cell differentiation represents a transition between two states of cellular activity-one in which cells proliferate and acquire information about their fates and identities, and another in which cells stop dividing and manifest the information gathered earlier.Many of the signaling pathways leading to cell differentiation depend on phosphorylation cascades. Mounting evidence points to signaling through MAP kinase (MAPK) pathways as a key component in this transition. Three distinct types of MAPK pathways have been identified: p42-p44 ERKs (extracellular signal-related kinases), p38 kinases, and p46-p54 JNKs (Jun N (amino)-terminal kinases). These major subfamilies transduce signals from different stimuli. The ERKs respond predominantly to growth factors and hormones and are activated in a Ras-dependent manner. The p38 and JNKs respond to different environmental stresses and are activated preferentially downstream of Rac1 and Cdc42 small G proteins (for review, see Canman and Kastan 1996). In most cases, MAPK activation is a transient event, even in the continuing presence of the stimulus that leads to its activation. MAPK activity is controlled by the balance of MAPK kinase and MAPK phosphatase activities.The dorsal closure of the Drosophila embryo provides an example of cell differentiation and how this is usually coupled to morphogenetic events and movements that shape late stages in development. Half way through embryogenesis, the dorsal surface of the embryo is covered by an extraembryonic membrane, the amnioserosa, which contacts the epidermis. After proliferation stops, the epidermis stretches dorsally and, as it encroaches the amnioserosa, closes the existing gap. Three phases lead to the successful completion of this event. The dorsalward movement of the epidermal cells, an anteroposterior stretching of the embryo and the seaming of the dorsal epidermis (Martinez-Arias 1993). The completion of this process takes several hours and is associated with specialized behavior of the dorsal-most epidermal cells. These cells display planar polarity reflected in the arrangement of the cytoskeleton, which is essential for the normal process...

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Regeneration following tissue damage often necessitates a mechanism for cellular reprogramming , so that surviving cells can give rise to all cell types originally found in the damaged tissue. This process, if unchecked, can also generate cell types that are inappropriate for a given location. We conducted a screen for genes that negatively regulate the frequency of notum-towing transformations following genetic ablation and regeneration of the wing pouch, from which we identified mutations in the transcriptional co-repressor C-terminal Binding Protein (CtBP). When CtBP function is reduced, ablation of the pouch can activate the JNK/AP-1 and JAK/STAT pathways in the notum to destabilize cell fates. Ectopic expression of Wingless and Dilp8 precede the formation of the ectopic pouch, which is subsequently generated by recruitment of both anterior and posterior cells near the compartment boundary. Thus, CtBP stabilizes cell fates following damage by opposing the destabilizing effects of the JNK/AP-1 and JAK/STAT pathways.

The fusion of epithelial sheets is an essential morphogenetic event. Here, we study the development of the abdomen of Drosophila as a model of bounded epithelia expansion and uncover a complex multistep process for the generation of the adult epidermis from histoblasts, founder cells that replace the larval cells during metamorphosis. We find that histoblasts experience a biphasic cell cycle and emit apical projections that direct their invasive planar intercalation in between larval cells. Coordinately, the larval cells extrude from the epithelia by apical constriction of an actomyosin ring and as a consequence die by apoptosis and are removed by circulating haemocytes. We demonstrate that the proliferation of histoblasts and the death of larval cells are triggered by two independent extrinsic Ecdysone hormonal pulses. Finally, we show that histoblast spreading and the death of larval cells depend on a mutual exchange of signals and are non-autonomous processes.