Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.
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RESEARCH ARTICLE|
10 January 2022
Mechanisms underlying the cooperation between loss of epithelial polarity and Notch signaling during neoplastic growth in Drosophila
Rémi Logeay,
Rémi Logeay
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
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Charles Géminard,
Charles Géminard
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
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Patrice Lassus
,
Patrice Lassus
2
IRCM, Inserm, Univ Montpellier, ICM, CNRS, Montpellier
, France
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Miriam Rodríguez-Vázquez,
Miriam Rodríguez-Vázquez
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
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Diala Kantar,
Diala Kantar
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
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Lisa Héron-Milhavet,
Lisa Héron-Milhavet
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
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Bettina Fischer,
Bettina Fischer
3
Dept. of Genetics, University of Cambridge, Cambridge
, United Kingdom
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Sarah J. Bray
,
Sarah J. Bray
4
Dept. of Physiology Development and Neuroscience, University of Cambridge, Cambridge
, United Kingdom
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Jacques Colinge
,
Jacques Colinge
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
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Alexandre Djiane
Alexandre Djiane
*
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
*Author for correspondence: alexandre.djiane@inserm.fr
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Rémi Logeay
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
Charles Géminard
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
Patrice Lassus
2
IRCM, Inserm, Univ Montpellier, ICM, CNRS, Montpellier
, France
Miriam Rodríguez-Vázquez
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
Diala Kantar
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
Lisa Héron-Milhavet
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
Bettina Fischer
3
Dept. of Genetics, University of Cambridge, Cambridge
, United Kingdom
Sarah J. Bray
4
Dept. of Physiology Development and Neuroscience, University of Cambridge, Cambridge
, United Kingdom
Jacques Colinge
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
Alexandre Djiane
*
1
IRCM, Inserm, Univ Montpellier, ICM, Montpellier
, France
*Author for correspondence: alexandre.djiane@inserm.fr
Received:
17 Aug 2021
Accepted:
17 Dec 2021
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Funding Group:
- Award Group:
- Funder(s): Agence Nationale de la Recherche
- Award Id(s): ANR-18-CE14-0041
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): Ligue Contre le Cancer
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): Fondation ARC pour la Recherche sur le Cancer
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): Medical Research Council
- Award Id(s): MR/L007177/1
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): European Union
- Award Id(s): PCIG13-GA-2013-618371
- Funder(s):
Development dev.200110.
Article history
Received:
17 Aug 2021
Accepted:
17 Dec 2021
Currently Viewing Accepted Manuscript - Newer Version Available
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Citation
Rémi Logeay, Charles Géminard, Patrice Lassus, Miriam Rodríguez-Vázquez, Diala Kantar, Lisa Héron-Milhavet, Bettina Fischer, Sarah J. Bray, Jacques Colinge, Alexandre Djiane; Mechanisms underlying the cooperation between loss of epithelial polarity and Notch signaling during neoplastic growth in Drosophila. Development 2022; dev.200110. doi: https://doi.org/10.1242/dev.200110
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