RRC ID 57329
Author Narbonne-Reveau K, Maurange C.
Title Developmental regulation of regenerative potential in Drosophila by ecdysone through a bistable loop of ZBTB transcription factors.
Journal PLoS Biol
Abstract In many organisms, the regenerative capacity of tissues progressively decreases as development progresses. However, the developmental mechanisms that restrict regenerative potential remain unclear. In Drosophila, wing imaginal discs become unable to regenerate upon damage during the third larval stage (L3). Here, we show that production of ecdysone after larvae reach their critical weight (CW) terminates the window of regenerative potential by acting on a bistable loop composed of two antagonistic Broad-complex/Tramtrack/Bric-à-brac Zinc-finger (ZBTB) genes: chinmo and broad (br). Around mid L3, ecdysone signaling silences chinmo and activates br to switch wing epithelial progenitors from a default self-renewing to a differentiation-prone state. Before mid L3, Chinmo promotes a strong regenerative response upon tissue damage. After mid L3, Br installs a nonpermissive state that represses regeneration. Transient down-regulation of ecdysone signaling or Br in late L3 larvae enhances chinmo expression in damaged cells that regain the capacity to regenerate. This work unveils a mechanism that ties the self-renewing and regenerative potential of epithelial progenitors to developmental progression.
Volume 17(2)
Pages e3000149
Published 2019-2-1
DOI 10.1371/journal.pbio.3000149
PMID 30742616
PMC PMC6386533
MeSH Aging / genetics* Animals Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Ecdysone / genetics Ecdysone / metabolism* Epithelial Cells / cytology Epithelial Cells / metabolism Gene Expression Regulation, Developmental Imaginal Discs / cytology Imaginal Discs / injuries Imaginal Discs / metabolism Larva / cytology Larva / growth & development Larva / metabolism Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Regeneration / genetics* Signal Transduction Stem Cells / cytology Stem Cells / metabolism Transcription Factors / genetics* Transcription Factors / metabolism Wings, Animal / cytology Wings, Animal / injuries Wings, Animal / metabolism
IF 8.386
Times Cited 3