Polyploidization and Cell Fusion Contribute to Wound Healing in the Adult Drosophila Epithelium

Abstract

Summary Background Re-establishing epithelial integrity and biosynthetic capacity is critically important following tissue damage. The adult Drosophila abdominal epithelium provides an attractive new system to address how post-mitotic diploid cells contribute to repair. Results Puncture wounds to the adult Drosophila epidermis close initially by forming a melanized scab. We found that epithelial cells near the wound site fuse to form a giant syncytium, which sends lamellae under the scab to re-epithelialize the damaged site. Other large cells arise more peripherally by initiating endocycles and becoming polyploid, or by cell fusion. Rac GTPase activity is needed for syncytium formation, while the Hippo signaling effector Yorkie modulates both polyploidization and cell fusion. Large cell formation is functionally important because when both polyploidization and fusion are blocked, wounds do not re-epithelialize. Conclusions Our observations indicate that cell mass lost upon wounding can be replaced by polyploidization instead of mitotic proliferation. We propose that large cells generated by polyploidization or cell fusion are essential because they are better able than diploid cells to mechanically stabilize wounds, especially those containing permanent acellular structures, such as scar tissue.

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing

“…While cell fusion, in combination with cell growth, is critically required for epidermal wound closure (Losick et al, 2013), whether too much cell fusion is harmful to proper wound healing is unclear. Our studies indicate that patches of big syncytia extending over a two-segment width in both anterior and posterior directions from the wound, however, do not impose immediate harm on the survival of an organism.…”

“…Cell fusion occurs during wound healing of the Drosophila larval and adult epidermis (Galko and Krasnow, 2004;Lesch et al, 2010;Losick et al, 2013). Here, cell fusion was proposed to help clear cellular debris (Galko and Krasnow, 2004) and, along with cell migration and growth, contribute to wound closure (Losick et al, 2013).…”

“…Here, cell fusion was proposed to help clear cellular debris (Galko and Krasnow, 2004) and, along with cell migration and growth, contribute to wound closure (Losick et al, 2013). Cell fusion is promoted by JNK pathway (JNK is also known as Basket in flies) activation, which appears to be mediated by disassembly of the integrin focal adhesion complex (Wang et al, 2015).…”

“…Cell fusion is promoted by JNK pathway (JNK is also known as Basket in flies) activation, which appears to be mediated by disassembly of the integrin focal adhesion complex (Wang et al, 2015). Cell fusion is also under the control of the Hippo pathway transcription factor Yki (Losick et al, 2013). More generally, the genetic mechanism of cell-cell fusion has been well characterized during Drosophila muscle differentiation.…”

Epidermal Wound Healing in the Nematode Caenorhabditis elegans

“…As the adult epidermis is composed of postmitotic syncytia, wounding does not (apparently) induce a proliferative response as in other models. In Drosophila, wounding can induce epidermal polyploidization 51 ; this has not yet been investigated in C. elegans.…”