Snail modulates JNK-mediated cell death in Drosophila

Wu, Chenxi; Li, Zhuojie; Xiang, Dongxi; Guo, Xiaowei; Sun, Ying; Wang, Xingjun; Hu, Yujia; Li, Tongtong; La, Xiaojin; Li, Jianing; Li, Jian; Li, Wenzhe; Xue, Lei

doi:10.1038/s41419-019-2135-7

Cited by 13 publications

(16 citation statements)

References 55 publications

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“…This was based on the RNA-Seq results, and we also validated these results using qPCR analysis (S3 Table and S7 Fig). Interestingly, the vertebrate Snail family proteins Snail1 and Snail2 regulate cell survival and apoptotic genes [89][90][91][92], and a recent study in Drosophila showed that snail specifically modulates the type of cell death mediated by c-Jun N-terminal Kinase [93]. Hence, Snail seems to partake in certain cell cycle events that are vital for normal growth of the endoreplicating tissue PG (endoreplication) as well as for cell death/survival.…”

Section: Snail As a Novel Regulator Of Endocycling In The Pgmentioning

confidence: 99%

Snail synchronizes endocycling in a TOR-dependent manner to coordinate entry and escape from endoreplication pausing during the Drosophila critical weight checkpoint

et al. 2020

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The final body size of any given individual underlies both genetic and environmental constraints. Both mammals and insects use target of rapamycin (TOR) and insulin signaling pathways to coordinate growth with nutrition. In holometabolous insects, the growth period is terminated through a cascade of peptide and steroid hormones that end larval feeding behavior and trigger metamorphosis, a nonfeeding stage during which the larval body plan is remodeled to produce an adult. This irreversible decision, termed the critical weight (CW) checkpoint, ensures that larvae have acquired sufficient nutrients to complete and survive development to adulthood. How insects assess body size via the CW checkpoint is still poorly understood on the molecular level. We show here that the Drosophila transcription factor Snail plays a key role in this process. Before and during the CW checkpoint, snail is highly expressed in the larval prothoracic gland (PG), an endocrine tissue undergoing endoreplication and primarily dedicated to the production of the steroid hormone ecdysone. We observed two Snail peaks in the PG, one before and one after the molt from the second to the third instar. Remarkably, these Snail peaks coincide with two peaks of PG cells entering S phase and a slowing of DNA synthesis between the peaks. Interestingly, the second Snail peak occurs at the exit of the CW checkpoint. Snail levels then decline continuously, and endoreplication becomes nonsynchronized in the PG after the CW checkpoint. This suggests that the synchronization of PG cells into S phase via Snail represents the mechanistic link used to terminate the CW checkpoint. Indeed, PG-specific loss of snail function prior to the CW checkpoint causes larval arrest due to a cessation of endoreplication in PG cells, whereas impairing snail after the CW checkpoint no longer affected endoreplication and further development. During the CW window, starvation or loss of TOR signaling disrupted the formation of Snail peaks and endocycle synchronization, whereas later starvation had no effect on snail expression. Taken together, our data demonstrate that insects use the TOR pathway to assess nutrient status during larval development to regulate Snail in ecdysone-producing cells as an effector protein to coordinate endoreplication and CW attainment.

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Section: Snail As a Novel Regulator Of Endocycling In The Pgmentioning

confidence: 99%

Snail synchronizes endocycling in a TOR-dependent manner to coordinate entry and escape from endoreplication pausing during the Drosophila critical weight checkpoint

et al. 2020

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“…The c-Jun N-terminal kinase (JNK) is a member of the highly conserved MAPKs family that plays pivotal roles in various cellular processes including apoptosis [11][12][13][14][15]. basket (bsk) encodes the sole Drosophila JNK that is phosphorylated and activated by the conserved upstream MAPK cascade, including the JNKK kinase dTAK1 and the JNK kinase Hemipterous (Hep) [16,17].…”

Section: Introductionmentioning

confidence: 99%

Toll signaling promotes JNK-dependent apoptosis in Drosophila

Xiang

et al. 2020

Cell Div

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Background: Apoptosis plays pivotal roles in organ development and tissue homeostasis, with its major function to remove unhealthy cells that may compromise the fitness of the organism. Toll signaling, with the ancient evolutionary origin, regulates embryonic dorsal-ventral patterning, axon targeting and degeneration, and innate immunity. Using Drosophila as a genetic model, we characterized the role of Toll signaling in apoptotic cell death. Results: We found that gain of Toll signaling is able to trigger caspase-dependent cell death in development. In addition, JNK activity is required for Toll-induced cell death. Furthermore, ectopic Toll expression induces the activation of JNK pathway. Moreover, physiological activation of Toll signaling is sufficient to produce JNK-dependent cell death. Finally, Toll signaling activates JNK-mediated cell death through promoting ROS production. Conclusions: As Toll pathway has been evolutionarily conserved from Drosophila to human, this study may shed light on the mechanism of mammalian Toll-like receptors (TLRs) signaling in apoptotic cell death.

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“…We counted the total number of migrating cells to quantify this phenotype and found that knockdown of Toll ‐ 7 resulted in decreased migrating cell number, while expression of Puc served as a positive control (Figure 1H–L, P). 44 Meanwhile, loss‐of‐ scrib also induced strong MMP1 expression, which is a biomarker for epithelial‐mesenchymal transition (EMT) 26,28,45 . Consistently, knockdown of Toll ‐ 7 suppressed scrib depletion‐induced MMP1 expression, while expression of Puc served as a positive control (Figure 1H’–L’, Q).…”

Section: Resultsmentioning

confidence: 71%

Toll‐7 promotes tumour growth and invasion in Drosophila

Xiang

Lin

et al. 2022

Cell Proliferation

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Objectives Drosophila melanogaster has become an excellent model organism to explore the genetic mechanisms underlying tumour progression. Here, by using well‐established Drosophila tumour models, we identified Toll‐7 as a novel regulator of tumour growth and invasion. Materials and methods Transgenic flies and genetic epistasis analysis were used. All flies were raised on a standard cornmeal and agar medium at 25°C unless otherwise indicated. Immunostaining and RT‐qPCR were performed by standard procedures. Images were taken by OLYMPUS BX51 microscope and Zeiss LSM 880 confocal microscope. Adobe Photoshop 2020 and Zeiss Zen were used to analyse the images. All results were presented in Scatter plots or Column bar graphs created by GraphPad Prism 8.0. Results Loss of Toll‐7 suppresses RasV12/lgl−/−‐induced tumour growth and invasion, as well as cell polarity disruption‐induced invasive cell migration, whereas expression of a constitutively active allele of Toll‐7 is sufficient to promote tumorous growth and cell migration. In addition, the Egr‐JNK signalling is necessary and sufficient for Toll‐7‐induced invasive cell migration. Mechanistically, Toll‐7 facilitates the endocytosis of Egr, which is known to activate JNK in the early endosomes. Moreover, Toll‐7 activates the EGFR‐Ras signalling, which cooperates with the Egr‐JNK signalling to promote Yki‐mediated cell proliferation and tissue overgrowth. Finally, Toll‐7 is necessary and sufficient for the proper maintenance of EGFR protein level. Conclusions Our findings characterized Toll‐7 as a proto‐oncogene that promotes tumour growth and invasion in Drosophila, which shed light on the pro‐tumour function of mammalian Toll‐like receptors (TLRs).

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Snail modulates JNK-mediated cell death in Drosophila

Cited by 13 publications

References 55 publications

Snail synchronizes endocycling in a TOR-dependent manner to coordinate entry and escape from endoreplication pausing during the Drosophila critical weight checkpoint

Snail synchronizes endocycling in a TOR-dependent manner to coordinate entry and escape from endoreplication pausing during the Drosophila critical weight checkpoint

Toll signaling promotes JNK-dependent apoptosis in Drosophila

Toll‐7 promotes tumour growth and invasion in Drosophila

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