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Publication

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

Tobias Reiff | Zeus A Antonello | Esther Ballesta-Illán | Laura Mira | Salvador Sala | Maria Navarro | Luis M Martinez | Maria Dominguez
The EMBO journal | 2019

The regenerative activity of adult stem cells carries a risk of cancer, particularly in highly renewable tissues. Members of the family of inhibitor of apoptosis proteins (IAPs) inhibit caspases and cell death, and are often deregulated in adult cancers; however, their roles in normal adult tissue homeostasis are unclear. Here, we show that regulation of the number of enterocyte-committed progenitor (enteroblast) cells in the adult Drosophila involves a caspase-mediated physiological apoptosis, which adaptively eliminates excess enteroblast cells produced by intestinal stem cells (ISCs) and, when blocked, can also lead to tumorigenesis. Importantly, we found that Diap1 is expressed by enteroblast cells and that loss and gain of Diap1 led to changes in enteroblast numbers. We also found that antagonistic interplay between Notch and EGFR signalling governs enteroblast life/death decisions via the Klumpfuss/WT1 and Lozenge/RUNX transcription regulators, which also regulate enteroblast differentiation and cell fate plasticity. These data provide new insights into how caspases drive adult tissue renewal and protect against the formation of tumours.

Pubmed ID: 31566767

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Associated grants

  • Agency: Fundación Científica Asociación Española Contra el Cáncer (AECC), International
    Id: AECC CICPF16001DOMÍ
  • Agency: Foundation Botin, International
  • Agency: MEC|Consejo Superior de Investigaciones Científicas (CSIC), International
    Id: MICCIN BFU2015-64239-R
  • Agency: Ministerio de Economía y Competitividad (MEC), International
    Id: SEV-2013-0317
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM084947
  • Agency: Generalitat Valenciana (Regional Government of Valencia), International
    Id: PROMETEO/2017/146
  • Agency: Deutsche Forschungsgesellschaft (DFG), International

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P{ry[+t7.2]=Act5C(FRT.polyA)lacZ.nls1}3, ry[506] (organism)

RRID:BDSC_6355

Drosophila melanogaster with name P{ry[+t7.2]=Act5C(FRT.polyA)lacZ.nls1}3, ry[506] from BDSC.

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w[*]; P{w[+mC]=GAL4-Hsp70.PB}2 (organism)

RRID:BDSC_2077

Drosophila melanogaster with name w[*]; P{w[+mC]=GAL4-Hsp70.PB}2 from BDSC.

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w[1118]; P{w[+mC]=QUAS-FLPo.P}1 (organism)

RRID:BDSC_30126

Drosophila melanogaster with name w[1118]; P{w[+mC]=QUAS-FLPo.P}1 from BDSC.

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w[*]; P{w[+mC]=UAS-Dronc.S}7/TM3, Sb[1] (organism)

RRID:BDSC_56197

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-Dronc.S}7/TM3, Sb[1] from BDSC.

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w[1118] (organism)

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Drosophila melanogaster with name w[1118] from BDSC.

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