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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Nutrition and PI3K/Akt signaling are required for p38-dependent regeneration

José Esteban-Collado1, Montserrat Corominas1, Florenci Serras1

  • 1Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona and Institute of Biomedicine of the University of Barcelona (IBUB), Diagonal 643, 08028 Barcelona, Spain.

Development (Cambridge, England)
|April 29, 2021
PubMed

Insights

Reactive oxygen species (ROS) trigger tissue repair. This study shows that Ask1 kinase, regulated by PI3K/Akt signaling and nutrient levels, controls p38 activation for regeneration in Drosophila wings.

Area of Science:

  • Cellular signaling pathways
  • Molecular mechanisms of regeneration
  • Drosophila melanogaster as a model organism

Background:

  • Tissue regeneration relies on early signaling events to initiate repair processes.
  • Reactive oxygen species (ROS) function as crucial early signals in damage response.
  • Mitogen-activated protein (MAP) kinase pathways, including Ask1, p38, and JNK, are implicated in cellular stress responses and regeneration.

Purpose of the Study:

  • To elucidate the role of PI3K/Akt signaling in Ask1-mediated regeneration.
  • To investigate the specific contribution of Ask1 to p38 and JNK activation during Drosophila wing regeneration.
  • To determine the influence of nutrient availability on Ask1-dependent regenerative signaling.

Main Methods:

  • Utilized the Drosophila wing regeneration model to study Ask1-dependent pathways.
  • Investigated the necessity of PI3K/Akt signaling for Ask1 to activate p38 and JNK.
  • Examined the impact of nutrient restriction and specific Ask1 mutations (Ser83) on regeneration.
  • Assessed the rescue effects of ectopic p38 or JNK activation.

Main Results:

  • PI3K/Akt signaling is essential for Ask1-mediated p38 activation, but not JNK activation, in Drosophila regeneration.
  • Nutrient restriction and mutation of Ser83 in Ask1 inhibit regeneration by interfering with PI3K/Akt-sensitive signaling.
  • Ectopic activation of p38, but not JNK, can rescue the regenerative defects caused by nutrient restriction or Ask1 mutations.
  • Ask1 controls p38 activation via Ser83, and this process is sensitive to nutrient levels.

Conclusions:

  • Ask1 regulates p38 activation through a PI3K/Akt-dependent and nutrient-sensitive mechanism involving Ser83.
  • This pathway is critical for distinguishing between pro-regenerative (p38) and pro-apoptotic (JNK) signaling outcomes.
  • The findings highlight a novel mechanism for nutrient sensing in controlling tissue repair and regenerative growth.
Keywords:
DrosophilaGrowthInsulinRegenerationSignaling

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