The NF-κB Factor Relish maintains blood progenitor homeostasis in the developing Drosophila lymph gland

PLoS Genet. 2024 Sep 9;20(9):e1011403. doi: 10.1371/journal.pgen.1011403. eCollection 2024 Sep.

Abstract

Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Using expression analyses, genetic manipulation and pharmacological approaches, we found that the Drosophila NF-κB transcription factor Relish (Rel) shields the progenitor pool from the metabolic pathway that inducts them into the differentiation program by curtailing the activation of JNK. Although ROS serves as the metabolic signal for progenitor differentiation, the input from ROS is monitored by the developmental signal TAK1, which is regulated by Relish. This developmental circuit ensures that the stockpile of ROS-primed progenitors is not exhausted entirely. Our study sheds light on how, during development, integrating NF-κB-like factors with metabolic pathways seem crucial to regulating cell fate transition during development.

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental
  • Hematopoiesis* / genetics
  • Homeostasis*
  • Larva* / genetics
  • Larva* / growth & development
  • Larva* / metabolism
  • Lymphoid Tissue / growth & development
  • Lymphoid Tissue / metabolism
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism
  • NF-kappa B* / genetics
  • NF-kappa B* / metabolism
  • Reactive Oxygen Species* / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Drosophila Proteins
  • Reactive Oxygen Species
  • NF-kappa B
  • Transcription Factors
  • Rel protein, Drosophila
  • MAP Kinase Kinase Kinases
  • TAK1 protein, Drosophila