Cell death-induced regeneration in wing imaginal discs requires JNK signalling

Abstract

SUMMARYRegeneration and tissue repair allow damaged or lost body parts to be replaced. After injury or fragmentation of Drosophila imaginal discs, regeneration leads to the development of normal adult structures. This process is likely to involve a combination of cell rearrangement and compensatory proliferation. However, the detailed mechanisms underlying these processes are poorly understood. We have established a system to allow temporally restricted induction of cell death in situ. Using Gal4/Gal80 and UASrpr constructs, targeted ablation of a region of the disc could be performed and regeneration monitored without the requirement for microsurgical manipulation. Using a ptc-Gal4 construct to drive rpr expression in the wing disc resulted in a stripe of dead cells in the anterior compartment flanking the anteroposterior boundary, whereas a sal-Gal4 driver generated a dead domain that includes both anterior and posterior cells. Under these conditions, regenerated tissues were derived from the damaged compartment, suggesting that compartment restrictions are preserved during regeneration. Our studies reveal that during regeneration the live cells bordering the domain in which cell death was induced first display cytoskeletal reorganisation and apical-to-basal closure of the epithelium. Then, proliferation begins locally in the vicinity of the wound and later more extensively in the affected compartment. Finally, we show that regeneration of genetically ablated tissue requires JNK activity. During cell death-induced regeneration, the JNK pathway is activated at the leading edges of healing tissue and not in the apoptotic cells, and is required for the regulation of healing and regenerative growth.

Identification of Novel Ras-Cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-Family/JNK Pathway Is a Central Driver of Tumorigenesis

“…Thus, RhoGEF2 and Rac1 require the activation of JNK to cooperate with Ras ACT to result in increased hyperplasia. A role for JNK in promoting proliferation has recently been revealed in tissue regeneration after wounding (Bergantinos et al 2010), and the SWH tissue growth control pathway has been implicated in this process (Grusche et al 2011;Sun and Irvine 2011). Whether the SWH pathway is also required for cooperation of JNK with Ras ACT to increase hyperplasia remains to be determined.…”

TIE-DYE: a combinatorial marking system to visualize and genetically manipulate clones during development in Drosophila melanogaster

“…Visualizing regenerative growth with TIE-DYE Regeneration in Drosophila imaginal discs can be observed either by damage in situ (Smith-Bolton et al, 2009;Bergantiños et al, 2010) or by culturing fragmented discs in the abdomens of adult females (Hadorn et al, 1949; reviewed by Worley et al, 2012). Imaginal discs regenerate by forming a blastema, which is an area of localized proliferation.…”

JAK/STAT signalling mediates cell survival in response to tissue stress

“…JNK activation is required for cytoskeletal rearrangement during wound closure (Ríos-Barrera and RiesgoEscovar, 2013;Bosch et al, 2005) and promotes elimination of damaged cells by injury-induced apoptosis (Bogoyevitch et al, 2010;Chen, 2012;Shlevkov and Morata, 2012;Luo et al, 2007;Moreno et al, 2002). Importantly, JNK drives compensatory proliferation to replace damaged tissues, through cell-autonomous (Bosch et al, 2008;Sun and Irvine, 2011;Grusche et al, 2011) and non-autonomous (Bergantinos et al, 2010;Mattila et al, 2005;Ryoo et al, 2004) mechanisms. A central question remaining unanswered is how these two different responses -proliferation and apoptosis -are brought into equilibrium downstream of JNK to restore tissue homeostasis.…”