Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
- Hilde-Mangold-Haus, University of Freiburg, Germany
- Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Germany
- Faculty of Biology, University of Freiburg, Germany
- International Max Planck Research School for Immunobiology, Epigenetics, and Metabolism, Germany
- CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Germany
- BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany
Figures
Figure 1 with 3 supplements
Apoptosis is essential to eliminate cells by interface surveillance.
(A) Wing disc illustration highlighting the pouch (dark gray), hinge (light gray), and notum (white), as well as characteristic folds (continuous lines) and dorso-ventral or anterior-posterior …
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Figure 1—source data 1
for Figure 1Q.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig1-data1-v3.xlsx
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Figure 1—source data 2
for Figure 1R.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig1-data2-v3.xlsx
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Figure 1—source data 3
for Figure 1S.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig1-data3-v3.xlsx
Figure 1—figure supplement 1
Apoptosis is essential to eliminate cells by interface surveillance.
(A and B) Schemes illustrating the key difference between the outcomes of two different tissue-intrinsic error correction mechanisms, namely classical cell-cell competition (A) and interface …
Figure 1—figure supplement 2
Apoptosis is essential to eliminate cells by interface surveillance.
(A, C, E, F, G, and H) Wing discs stained to visualize endogenous patterns of Forkhead (Fkh) (A) and Eyeless (Ey) expression (C), Dpp-signaling (Dad4-LacZ, a Dpp target gene) (E), Wg-signaling …
Figure 1—figure supplement 3
Apoptosis is essential to eliminate cells by interface surveillance.
(A) Distribution of the relative percentage of apoptotic area in individual fkh-expressing clones plotted against clone size. A non-linear regression analysis and a correlation analysis using …
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Figure 1—figure supplement 3—source data 1
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig1-figsupp3-data1-v3.xlsx
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Figure 1—figure supplement 3—source data 2
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig1-figsupp3-data2-v3.xlsx
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Figure 1—figure supplement 3—source data 3
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig1-figsupp3-data3-v3.xlsx
Figure 2 with 2 supplements
Interface surveillance activates bilateral JNK interface signaling.
(A, B, D, and E) Wing discs carrying mosaic clones (magenta or gray) expressing GFP (A and B) or fkh (D and E), as well as the JNK reporter TRE-RFP (green or gray). Discs were stained with DAPI to …
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Figure 2—source data 1
for Figure 2I.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig2-data1-v3.xlsx
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Figure 2—source data 2
for Figure 2J.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig2-data2-v3.xlsx
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Figure 2—source data 3
for Figure 2K.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig2-data3-v3.xlsx
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Figure 2—source data 4
for Figure 2L.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig2-data4-v3.xlsx
Figure 2—figure supplement 1
JNK interface signaling is a robust hallmark of interface surveillance responses.
(A and C) Lateral section of a wing disc expressing the TRE-RFP reporter (gray or green) and carrying mosaic clones expressing ey (gray or magenta) in minority topology (A) where clones are …
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Figure 2—figure supplement 1—source data 1
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig2-figsupp1-data1-v3.xlsx
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Figure 2—figure supplement 1—source data 2
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig2-figsupp1-data2-v3.xlsx
Figure 2—figure supplement 2
Interface JNK signaling can be detected using the puc-LacZ reporter.
(A–D) Lateral section of wing discs expressing the alternative JNK-reporter puc-LacZ (gray or green) and carrying mosaic clones (gray or magenta) expressing GFP (A), fkh (B), ey (C), or RasV12 (D). …
Figure 3 with 1 supplement
JNK activation is not dependent on JNK activation in the adjacent interface cell.
(A–F) Wing discs carrying mosaic clones (magenta or gray) expressing BskDN (A and D), Ey (B and E), or BskDN, Ey (C and F) and expressing the JNK reporter TRE-RFP (gray or green). Discs were stained …
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Figure 3—source data 1
for Figure 3G.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig3-data1-v3.xlsx
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Figure 3—source data 2
for Figure 3H.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig3-data2-v3.xlsx
Figure 3—figure supplement 1
JNK activation is not dependent on JNK activation in the adjacent interface cell.
(A and B) Wing discs carrying mosaic control clones (magenta or gray) expressing GFP and also expressing the JNK-reporter TRE-RFP (gray or green). Discs were stained with DAPI to visualize …
Figure 4 with 2 supplements
JNK interface signaling is unique to interface surveillance and is not activated by cell competition.
(A, B, and D) Wing disc carrying mosaic clones (gray or magenta) expressing GFP (A), Myc (B, winner), or GFP-labeled clones heterozygous mutant for RpS3 (D, loser). Discs express the JNK reporter …
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Figure 4—source data 1
for Figure 4C.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig4-data1-v3.xlsx
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Figure 4—source data 2
for Figure 4E.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig4-data2-v3.xlsx
Figure 4—figure supplement 1
JNK interface signaling is not activated by cell competition.
(A and B) Lateral sections of wing discs expressing the TRE-RFP reporter (gray or green) and carrying mosaic clones (gray or magenta) expressing GFP (A), or a wts-RNAi construct (B). Scale bar = 50 …
Figure 4—figure supplement 2
JNK signaling is not required for actomyosin enrichment at clonal interfaces.
(A, B, C, and D) Lateral sections of wing discs carrying mosaic clones (gray or magenta) expressing ey (A), tkvCA (C) or BskDN, ey (B), BskDN, tkvCA (D). Discs were stained with Phalloidin to …
Figure 5 with 1 supplement
Cell elimination at clonal interfaces is mediated by JNK.
(A) Maximum-intensity projection of basal sections from a wing imaginal disc carrying clones (magenta) expressing fkh and stained for cleaved Dcp1 (cDcp1) to visualize apoptosis (green). Colored …
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Figure 5—source data 1
for Figure 5B.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig5-data1-v3.xlsx
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Figure 5—source data 2
for Figure 5H.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig5-data2-v3.xlsx
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Figure 5—source data 3
for Figure 5L.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig5-data3-v3.xlsx
Figure 5—figure supplement 1
Apoptosis can be observed at the buckling points of fkh expressing clones.
(A) Example of a segmentation mask based on clone areas (white), and ROIs (regions of interest) corresponding to wild-type interface cells (cyan boundary) and clonal interface cells (magenta …
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Figure 5—figure supplement 1—source data 1
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig5-figsupp1-data1-v3.xlsx
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Figure 5—figure supplement 1—source data 2
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig5-figsupp1-data2-v3.xlsx
Figure 6 with 1 supplement
Bilateral JNK-signaling and apoptosis scale with clone size.
(A–C) Quantification of TRE-RFP intensity within the entire clone area (A), only within clonal interface cells (B) and only within wild-type interface cells (C) in mosaic discs with fkh-expressing …
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Figure 6—source data 1
for Figure 6A.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-data1-v3.xlsx
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Figure 6—source data 2
for Figure 6B.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-data2-v3.xlsx
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Figure 6—source data 3
for Figure 6C.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-data3-v3.xlsx
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Figure 6—source data 4
for Figure 6E.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-data4-v3.xlsx
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Figure 6—source data 5
for Figure 6F.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-data5-v3.xlsx
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Figure 6—source data 6
for Figure 6G.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-data6-v3.xlsx
Figure 6—figure supplement 1
Bilateral JNK-activity scales with clone size.
(A) Topology of interface contacts depending on size of ‘clones’ (i.e. Fate 2). Numbers denote the number of contacts with cells of the other genotype. The ratio of cell contacts changes with …
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Figure 6—figure supplement 1—source data 1
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-figsupp1-data1-v3.xlsx
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Figure 6—figure supplement 1—source data 2
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig6-figsupp1-data2-v3.xlsx
Figure 7 with 2 supplements
Cell elimination by interface surveillance is suppressed by oncogenic RasV12.
(A) Wing disc carrying mosaic clones (magenta) expressing RasV12 were stained with phalloidin to visualize Actin (gray or green). Yellow frames mark regions shown in (A’). Yellow arrows point to …
Figure 7—figure supplement 1
RasV12 dominantly induces high-ERK signaling in fkh- and Ey-expressing clones.
(A) Scheme illustrating how the miniCic ERK-reporter works. Nuclear localization of the miniCic reporter indicates low-ERK signaling, and cytoplasmic localization indicates high-ERK signaling. (B–D …
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Figure 7—figure supplement 1—source data 1
for Figure 7—figure supplement 1E fkh.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig7-figsupp1-data1-v3.xlsx
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Figure 7—figure supplement 1—source data 2
for Figure 7—figure supplement 1E–R as-fkh.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig7-figsupp1-data2-v3.xlsx
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Figure 7—figure supplement 1—source data 3
for Figure 7—figure supplement 1E–R as.
- https://cdn.elifesciences.org/articles/80809/elife-80809-fig7-figsupp1-data3-v3.xlsx
Figure 7—figure supplement 2
RasV12 rescues ey-expressing clones from apoptosis.
(A–C) Maximum intensity projection of basal sections of wing discs carrying mosaic clones (magenta) expressing RasV12 (A) or ey (B) or ey,RasV12 (C). Discs were stained for cDcp1 (gray or green) to …
Additional files
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Supplementary file 1
Fly strains.
Table listing fly strains used in this study.
- https://cdn.elifesciences.org/articles/80809/elife-80809-supp1-v3.docx
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Supplementary file 2
Detailed genotypes.
Table listing detailed genotypes per figure panels
- https://cdn.elifesciences.org/articles/80809/elife-80809-supp2-v3.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/80809/elife-80809-mdarchecklist1-v3.pdf
