Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila
Abstract 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...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Reiff, Tobias [verfasserIn] Antonello, Zeus A [verfasserIn] Ballesta‐Illán, Esther [verfasserIn] Mira, Laura [verfasserIn] Sala, Salvador [verfasserIn] Navarro, Maria [verfasserIn] Martinez, Luis M [verfasserIn] Dominguez, Maria [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2019 |
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| Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 38(2019), 21 vom: 30. Sept. |
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| Übergeordnetes Werk: |
volume:38 ; year:2019 ; number:21 ; day:30 ; month:09 |
| Links: |
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| DOI / URN: |
10.15252/embj.2018101346 |
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| Katalog-ID: |
SPR058016694 |
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| 100 | 1 | |a Reiff, Tobias |e verfasserin |0 (orcid)0000-0001-6610-6148 |4 aut | |
| 245 | 1 | 0 | |a Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila |
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| 520 | |a Abstract 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. | ||
| 520 | |a Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. | ||
| 520 | |a Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. | ||
| 650 | 4 | |a caspase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a intestinal enteroblast |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Klumpfuss/WT1 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Lozenge/RUNX |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a physiological apoptosis |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Antonello, Zeus A |e verfasserin |0 (orcid)0000-0002-5933-6794 |4 aut | |
| 700 | 1 | |a Ballesta‐Illán, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Mira, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Sala, Salvador |e verfasserin |4 aut | |
| 700 | 1 | |a Navarro, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Luis M |e verfasserin |4 aut | |
| 700 | 1 | |a Dominguez, Maria |e verfasserin |0 (orcid)0000-0002-3329-7862 |4 aut | |
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10.15252/embj.2018101346 doi (DE-627)SPR058016694 (SPR)embj.2018101346-e DE-627 ger DE-627 rakwb eng Reiff, Tobias verfasserin (orcid)0000-0001-6610-6148 aut Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. caspase (dpeaa)DE-He213 intestinal enteroblast (dpeaa)DE-He213 Klumpfuss/WT1 (dpeaa)DE-He213 Lozenge/RUNX (dpeaa)DE-He213 physiological apoptosis (dpeaa)DE-He213 Antonello, Zeus A verfasserin (orcid)0000-0002-5933-6794 aut Ballesta‐Illán, Esther verfasserin aut Mira, Laura verfasserin aut Sala, Salvador verfasserin aut Navarro, Maria verfasserin aut Martinez, Luis M verfasserin aut Dominguez, Maria verfasserin (orcid)0000-0002-3329-7862 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 38(2019), 21 vom: 30. Sept. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:38 year:2019 number:21 day:30 month:09 https://dx.doi.org/10.15252/embj.2018101346 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 38 2019 21 30 09 |
| spelling |
10.15252/embj.2018101346 doi (DE-627)SPR058016694 (SPR)embj.2018101346-e DE-627 ger DE-627 rakwb eng Reiff, Tobias verfasserin (orcid)0000-0001-6610-6148 aut Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. caspase (dpeaa)DE-He213 intestinal enteroblast (dpeaa)DE-He213 Klumpfuss/WT1 (dpeaa)DE-He213 Lozenge/RUNX (dpeaa)DE-He213 physiological apoptosis (dpeaa)DE-He213 Antonello, Zeus A verfasserin (orcid)0000-0002-5933-6794 aut Ballesta‐Illán, Esther verfasserin aut Mira, Laura verfasserin aut Sala, Salvador verfasserin aut Navarro, Maria verfasserin aut Martinez, Luis M verfasserin aut Dominguez, Maria verfasserin (orcid)0000-0002-3329-7862 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 38(2019), 21 vom: 30. Sept. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:38 year:2019 number:21 day:30 month:09 https://dx.doi.org/10.15252/embj.2018101346 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 38 2019 21 30 09 |
| allfields_unstemmed |
10.15252/embj.2018101346 doi (DE-627)SPR058016694 (SPR)embj.2018101346-e DE-627 ger DE-627 rakwb eng Reiff, Tobias verfasserin (orcid)0000-0001-6610-6148 aut Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. caspase (dpeaa)DE-He213 intestinal enteroblast (dpeaa)DE-He213 Klumpfuss/WT1 (dpeaa)DE-He213 Lozenge/RUNX (dpeaa)DE-He213 physiological apoptosis (dpeaa)DE-He213 Antonello, Zeus A verfasserin (orcid)0000-0002-5933-6794 aut Ballesta‐Illán, Esther verfasserin aut Mira, Laura verfasserin aut Sala, Salvador verfasserin aut Navarro, Maria verfasserin aut Martinez, Luis M verfasserin aut Dominguez, Maria verfasserin (orcid)0000-0002-3329-7862 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 38(2019), 21 vom: 30. Sept. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:38 year:2019 number:21 day:30 month:09 https://dx.doi.org/10.15252/embj.2018101346 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 38 2019 21 30 09 |
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10.15252/embj.2018101346 doi (DE-627)SPR058016694 (SPR)embj.2018101346-e DE-627 ger DE-627 rakwb eng Reiff, Tobias verfasserin (orcid)0000-0001-6610-6148 aut Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. caspase (dpeaa)DE-He213 intestinal enteroblast (dpeaa)DE-He213 Klumpfuss/WT1 (dpeaa)DE-He213 Lozenge/RUNX (dpeaa)DE-He213 physiological apoptosis (dpeaa)DE-He213 Antonello, Zeus A verfasserin (orcid)0000-0002-5933-6794 aut Ballesta‐Illán, Esther verfasserin aut Mira, Laura verfasserin aut Sala, Salvador verfasserin aut Navarro, Maria verfasserin aut Martinez, Luis M verfasserin aut Dominguez, Maria verfasserin (orcid)0000-0002-3329-7862 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 38(2019), 21 vom: 30. Sept. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:38 year:2019 number:21 day:30 month:09 https://dx.doi.org/10.15252/embj.2018101346 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 38 2019 21 30 09 |
| allfieldsSound |
10.15252/embj.2018101346 doi (DE-627)SPR058016694 (SPR)embj.2018101346-e DE-627 ger DE-627 rakwb eng Reiff, Tobias verfasserin (orcid)0000-0001-6610-6148 aut Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. caspase (dpeaa)DE-He213 intestinal enteroblast (dpeaa)DE-He213 Klumpfuss/WT1 (dpeaa)DE-He213 Lozenge/RUNX (dpeaa)DE-He213 physiological apoptosis (dpeaa)DE-He213 Antonello, Zeus A verfasserin (orcid)0000-0002-5933-6794 aut Ballesta‐Illán, Esther verfasserin aut Mira, Laura verfasserin aut Sala, Salvador verfasserin aut Navarro, Maria verfasserin aut Martinez, Luis M verfasserin aut Dominguez, Maria verfasserin (orcid)0000-0002-3329-7862 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 38(2019), 21 vom: 30. Sept. (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:38 year:2019 number:21 day:30 month:09 https://dx.doi.org/10.15252/embj.2018101346 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 38 2019 21 30 09 |
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Enthalten in The EMBO Journal 38(2019), 21 vom: 30. Sept. volume:38 year:2019 number:21 day:30 month:09 |
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Enthalten in The EMBO Journal 38(2019), 21 vom: 30. Sept. volume:38 year:2019 number:21 day:30 month:09 |
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caspase intestinal enteroblast Klumpfuss/WT1 Lozenge/RUNX physiological apoptosis |
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Reiff, Tobias @@aut@@ Antonello, Zeus A @@aut@@ Ballesta‐Illán, Esther @@aut@@ Mira, Laura @@aut@@ Sala, Salvador @@aut@@ Navarro, Maria @@aut@@ Martinez, Luis M @@aut@@ Dominguez, Maria @@aut@@ |
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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.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">caspase</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">intestinal enteroblast</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Klumpfuss/WT1</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Lozenge/RUNX</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">physiological apoptosis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Antonello, Zeus A</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-5933-6794</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ballesta‐Illán, Esther</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mira, Laura</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sala, Salvador</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Navarro, Maria</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Martinez, Luis M</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dominguez, Maria</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-3329-7862</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">The EMBO Journal</subfield><subfield code="d">Nature Publishing Group UK, 2023</subfield><subfield code="g">38(2019), 21 vom: 30. 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|
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Reiff, Tobias |
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Reiff, Tobias misc caspase misc intestinal enteroblast misc Klumpfuss/WT1 misc Lozenge/RUNX misc physiological apoptosis Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila |
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Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila caspase (dpeaa)DE-He213 intestinal enteroblast (dpeaa)DE-He213 Klumpfuss/WT1 (dpeaa)DE-He213 Lozenge/RUNX (dpeaa)DE-He213 physiological apoptosis (dpeaa)DE-He213 |
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Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila |
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Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila |
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Reiff, Tobias Antonello, Zeus A Ballesta‐Illán, Esther Mira, Laura Sala, Salvador Navarro, Maria Martinez, Luis M Dominguez, Maria |
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notch and egfr regulate apoptosis in progenitor cells to ensure gut homeostasis in drosophila |
| title_auth |
Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila |
| abstract |
Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. © The Author(s) 2019 |
| abstractGer |
Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. © The Author(s) 2019 |
| abstract_unstemmed |
Abstract 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. Synopsis The rate of intestinal epithelium turnover is adjusted to the level of damage incurred by the tissue. In the Drosophila gut, DIAP1‐regulated apoptosis of committed progenitor cells regulates tissue homeostasis under conditions of slow intestinal cell replacement. Intestinal stem cell proliferation remains constant under conditions of reduced intestinal epithelium turnover.Adjustment of differentiated cell production is regulated by intestinal progenitor cell apoptosis.Antagonistic activity of Notch and EGFR signaling pathways in enteroblasts controls the differentiation/cell death decision.EGFR and Notch signaling regulates DIAP1 levels in enteroblasts.In enteroblasts, Lozenge/Runx and Klumpfuss/WT1 mediate cell death, lineage maintenance, and differentiation downstream of Notch. Graphical Abstract The rate of steady‐state turnover in the Drosophila intestinal epithelium is adjusted via DIAP1‐regulated apoptosis of committed progenitor cells. © The Author(s) 2019 |
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Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila |
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Antonello, Zeus A Ballesta‐Illán, Esther Mira, Laura Sala, Salvador Navarro, Maria Martinez, Luis M Dominguez, Maria |
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| score |
7.400794 |