JNK signaling pathway required for wound healing in regenerating Drosophila wing imaginal discs

Abstract

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.

Delayed Inhibition of c-Jun N-Terminal Kinase Worsens Outcomes after Focal Cerebral Ischemia

“…In many systems, ranging from insects to mammals, JNK plays diverse roles in organ development and tissue repair. In Drosophila, JNK homologs contribute to cell proliferation and wound healing (Bosch et al, 2005). In Caenorhabditis elegans, JNK homologs participate in normal development as well as in stress response after injury (Mizuno et al, 2004).…”

Drosophila as a model of wound healing and tissue regeneration in vertebrates

“…Indeed columnar and peripodial epithelial cells in the disc form a contractile actin cable and filopodia in the wound edges, thus closing the wound as in DC (Fig. 5B,C) (Bosch et al, 2005;Mattila et al, 2005). Later a blastema is formed (Abbott et al, 1981;Kiehle Fig.…”

“…Picture reprinted from Rauzi and Lecuit (2009) with permission from Elsevier. and Schubiger, 1985;Bosch et al, 2005;Bergantiñ os et al, 2010a). The blastema cells in Drosophila imaginal discs are not pluripotent and retain their compartment origin identity, contributing only to the reconstruction of the damaged compartment (Bosch et al, 2008;Bergantiñ os et al, 2010a).…”

“…Recently, Wagner and co-workers provided evidence that neoblasts, which are adult pluripotent stem cells, underlie the remarkable regenerative abilities of planarians (Wagner et al, 2011 Table 1 in Stocum and Zupanc, 2008). Although different, all these processes share signaling pathways and molecular mechanisms to restore normal function of the affected tissue (Bosch et al, 2005;Mattila et al, 2005;Gurtner et al, 2008). Determining how common signaling pathways are used in different processes is one of the main questions in developmental biology and regenerative medicine.…”

Epithelial delamination and migration

“…22 In this period of non-responsiveness to wound signals embryonic tissues can still repair and they do so generally without producing scarring or fibrosis, suggesting the intriguing idea that scars are the result of the inflammatory process that takes place at the adults wounds. 25 Beyond their roles in the embryo, Drosophila hemocytes play an important role in efficiently fighting infections 26 and repairing tissue damage [27][28][29] during the larval and adult stages of the fly. Just before hatching into larva, the heart (dorsal vessel) begins to beat, and the hemolymph (fly blood) circulation is established.…”