Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila

Tobias Reiff1, Zeus A Antonello1, Esther Ballesta-Illán1

  • 1Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Alicante, Spain.

The EMBO Journal
|October 1, 2019
PubMed

Insights

Adult stem cell renewal involves programmed cell death to prevent cancer. Inhibitor of apoptosis proteins (IAPs) like Diap1 regulate this process, maintaining tissue homeostasis and preventing tumor formation.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Adult stem cells drive tissue renewal but carry cancer risk, especially in highly regenerative tissues.
  • Inhibitor of apoptosis proteins (IAPs) regulate cell death but their role in normal tissue homeostasis is not fully understood.
  • Deregulation of IAPs is common in adult cancers.

Purpose of the Study:

  • To investigate the role of caspase-mediated apoptosis in regulating adult tissue homeostasis.
  • To elucidate the function of Inhibitor of Apoptosis Proteins (IAPs) in adult tissue renewal and cancer prevention.
  • To understand the signaling pathways governing progenitor cell survival and differentiation.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism for studying adult tissue renewal.
  • Investigated the expression and function of Diap1 in enteroblast cells.
  • Analyzed the interplay between Notch and EGFR signaling pathways, and their downstream transcription factors (Klumpfuss/WT1, Lozenge/RUNX).

Main Results:

  • Caspase-mediated physiological apoptosis regulates enteroblast progenitor cell numbers in adult Drosophila.
  • Blocking this apoptosis leads to tumorigenesis.
  • Diap1 is expressed in enteroblast cells, and its levels influence enteroblast numbers.
  • Notch and EGFR signaling antagonistically control enteroblast life/death decisions and differentiation via specific transcription regulators.

Conclusions:

  • Caspase activity is crucial for adult tissue renewal and cancer protection.
  • Diap1 plays a key role in regulating progenitor cell populations.
  • The interplay of signaling pathways and transcription factors governs progenitor cell fate and tissue homeostasis.

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