Size compensation in Drosophila after generalised cell death

Abstract

Regeneration is a response mechanism to restore tissues that have been damaged or lost by mechanical or physiological insults. We are studying in the wing imaginal disc of Drosophila the regenerative response to a high dose of Ionizing Radiation (IR), which we estimate kills at least 35% of the cells. After such treatment irradiated discs are able to restore normal size and shape, indicating there is a mechanism to replace the lost cells. We have tested the role of the Jun N-terminal Kinase (JNK), Janus Kinase (JAK/STAT) and Wingless (Wg) pathways, which have been shown to promote cell proliferation in regenerating tissues. We find that there is size compensation after IR in the absence of function of these pathways, strongly suggesting that they are not necessary for the compensation. We also find that the proliferation rate is not increased after IR. We argue that after generalized death caused by IR there is not a specific mechanism to promote cell proliferation. The irradiated discs suffer a developmental delay and then resume growth at normal rate until they reach the final stereotyped size. The delay appears to be associated with a developmental reversion, as irradiated discs undergo rejuvenation towards an earlier developmental stage. The response to generalized damage is fundamentally different from that to localized damage, which requires activity of JNK and Wg.