Epithelial cell-turnover ensures robust coordination of tissue growth in Drosophila ribosomal protein mutants

PLoS Genet. 2021 Jan 28;17(1):e1009300. doi: 10.1371/journal.pgen.1009300. eCollection 2021 Jan.

Abstract

Highly reproducible tissue development is achieved by robust, time-dependent coordination of cell proliferation and cell death. To study the mechanisms underlying robust tissue growth, we analyzed the developmental process of wing imaginal discs in Drosophila Minute mutants, a series of heterozygous mutants for a ribosomal protein gene. Minute animals show significant developmental delay during the larval period but develop into essentially normal flies, suggesting there exists a mechanism ensuring robust tissue growth during abnormally prolonged developmental time. Surprisingly, we found that both cell death and compensatory cell proliferation were dramatically increased in developing wing pouches of Minute animals. Blocking the cell-turnover by inhibiting cell death resulted in morphological defects, indicating the essential role of cell-turnover in Minute wing morphogenesis. Our analyses showed that Minute wing discs elevate Wg expression and JNK-mediated Dilp8 expression that causes developmental delay, both of which are necessary for the induction of cell-turnover. Furthermore, forced increase in Wg expression together with developmental delay caused by ecdysone depletion induced cell-turnover in the wing pouches of non-Minute animals. Our findings suggest a novel paradigm for robust coordination of tissue growth by cell-turnover, which is induced when developmental time axis is distorted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Ecdysone / genetics
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Imaginal Discs / growth & development*
  • Imaginal Discs / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Larva / genetics
  • Larva / growth & development
  • Metamorphosis, Biological / genetics
  • Organogenesis / genetics
  • Ribosomal Proteins / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Wings, Animal / growth & development
  • Wings, Animal / metabolism
  • Wnt1 Protein / genetics*

Substances

  • Drosophila Proteins
  • Intercellular Signaling Peptides and Proteins
  • Ribosomal Proteins
  • Transcription Factors
  • Wnt1 Protein
  • insulin-like peptide 8, Drosophila
  • wg protein, Drosophila
  • Ecdysone

Grants and funding

This work was supported by Grant-in-Aid for Scientific Research (A) (Grant No. 16H02505) to T.I, Grant-in-Aid for Scientific Research on Innovative Areas (Grant Nos. 15H05862, 26114002, 20H04866) to S.O and T.I, Grant-in-Aid for challenging Exploratory Research (Grant No. 19K22423) to S.O, the Naito Foundation to S.O and T.I, the Takeda Science Foundation to S.O and T.I, Japan Agency for Medical Research and Development (Project for Elucidating and Controlling Mechanisms of Aging and Longevity, Grant Number 17938731) to T.I., Inamori Foundation to S.O., Toray Science Foundation to S.O., Senri Life Science Foundation to S.O., Yamada Science Foundation to S.O. and the Mitsubishi Foundation to S.O. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.