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Updated: Sep 12, 2025

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A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration

John W Quinn1, Mariah C Lee1, Chloe Van Hazel1

  • 1School of Life Sciences, Arizona State University, 427 E Tyler Mall LSE 229, Tempe, AZ 85287-4501, USA.

Development (Cambridge, England)
|August 7, 2025
PubMed

Insights

Regeneration relies on coordinated gene activation. This study reveals how JNK and JAK/STAT signaling pathways collaborate to control gene expression via damage-responsive enhancers for effective tissue repair.

Area of Science:

  • Developmental Biology
  • Regenerative Medicine
  • Molecular Biology

Background:

  • Tissue regeneration involves complex gene regulation, often re-utilizing developmental pathways.
  • The precise initiation and spatial control of gene expression post-injury remain key unanswered questions.
  • Stress-activated MAP kinase JNK is crucial for regeneration in Drosophila, but its target selectivity is unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which JNK signaling initiates and regulates gene expression during tissue regeneration.
  • To identify the downstream factors and enhancers involved in JNK-mediated gene activation.
  • To understand how JNK signaling is spatially controlled to ensure proper regenerative outcomes.

Main Methods:

  • Utilized Drosophila as a model organism to study regeneration.
  • Investigated the role of Damage-Responsive, Maturity-Silenced (DRMS) enhancers in JNK-driven gene expression.
  • Analyzed the interplay between JNK, JAK/STAT signaling, and enhancer activity in damaged tissues.

Main Results:

  • Cell death is not required for the activation of DRMS enhancers; activation depends solely on JNK and its effectors.
  • JAK/STAT signaling acts as a crucial secondary input, expanding enhancer activity to the wound periphery.
  • A specific threshold level of JNK activity is necessary to trigger enhancer activation.

Conclusions:

  • JNK and JAK/STAT signaling pathways cooperate to achieve spatially and temporally regulated gene expression through DRMS enhancers.
  • This coordinated signaling ensures appropriate gene activation for successful tissue regeneration.
  • Findings provide insights into the molecular mechanisms governing regenerative processes.
Keywords:
DrosophilaEnhancerGene regulationJAK/STATJNKRegeneration

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