In a study published in PLOS Biology, Karine Narbonne-Reveau and Cédric Maurange identify a signalling pathway that puts an end to the regeneration capacity of embryonic tissues in Drosophila.
While some organisms exhibit remarkable regenerative abilities throughout their life, many animals, including mammals, present limited regenerative potential that progressively decreases during development. Understanding the mechanisms underlying this progressive loss is important to devise therapeutic approaches aiming at facilitating the regeneration of a damaged tissue throughout life. The fruitfly Drosophila is a powerful model organism to address such questions. Indeed, while tissues, such as imaginal discs, can fully regenerate if damaged during early development, they fail to do so upon damages during late development. We show here that restriction of regenerative potential occurring during midlarval stages is due to the production of a steroid hormone, named ecdysone. By genetically manipulating ecdysone signaling, we can uncouple regenerative abilities from developmental progression. In particular, we show that ecdysone signaling triggers a switch in the sequential expression of two transcription factors, Chinmo and Broad, that positively and negatively regulate the competence for imaginal disc regeneration, respectively. Our work therefore identifies a key developmental signal that restricts regenerative potential in insects and opens new perspectives on elucidating how regeneration-permissive transcriptional programs are locked as development progresses.
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Developmental regulation of regenerative potential in Drosophila by ecdysone through a bistable loop of ZBTB transcription factors
Karine Narbonne-Reveau, Cédric Maurange
PLoS Biol. 2019 Feb 11;17(2):e3000149. doi: 10.1371/journal.pbio.3000149. eCollection 2019 Feb.