Journal
DEVELOPMENT
Volume 149, Issue 3, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.200110
Keywords
Notch signaling; Drosophila; Epithelial polarity; Neoplasia
Categories
Funding
- Medical Research Council (MRC) [MR/L007177/1]
- Ligue Contre le Cancer
- Fondation ARC pour la Recherche sur le Cancer
- Fondation ARC pour la Recherche sur le Cancer, a Marie Curie Career Integration Grant [PCIG13-GA-2013-618371]
- Agence Nationale de la Recherche [ANR-18-CE14-0041]
- Agence Nationale de la Recherche (ANR) [ANR-18-CE14-0041] Funding Source: Agence Nationale de la Recherche (ANR)
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This study investigates the activity changes of the Notch pathway in Drosophila wing disc epithelial growth according to the polarity status of cells. The results show that the scrib mutation affects the transcriptional output of the Notch pathway, but not the global distribution of the Notch-dedicated transcription factor. Furthermore, it is found that a group of transcription factors is required for Notch-dependent neoplasms. Additionally, the study highlights some specificities of Notch/schb, such as the role of PAR domain-containing basic leucine zipper transcription factors and Notch direct target genes in neoplastic growth.
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 (scab 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 Rasiscrib neoplasm (namely AP-1, Stat92E, Ftz-F1 and basic leucine zipper factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally, our work highlights some Notch/schb specificities, in particular the role of the PAR domain-containing basic leucine zipper transcription factor and Notch direct target Pdp1 for neoplastic growth.
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