Dataset Information

The Dpp/TGF?-dependent corepressor Schnurri protects epithelial cells from JNK-induced apoptosis in drosophila embryos.

ABSTRACT: Jun N-terminal kinase (JNK) often mediates apoptosis in response to cellular stress. However, during normal development, JNK signaling controls a variety of live cell behaviors, such as during dorsal closure in Drosophila embryos. During this process, the latent proapoptotic activity of JNK becomes apparent following Dpp signaling suppression, which leads to JNK-dependent transcriptional activation of the proapoptotic gene reaper. Dpp signaling also protects cells from JNK-dependent apoptosis caused by epithelial disruption. We find that repression of reaper transcription by Dpp is mediated by Schnurri. Moreover, reporter gene analysis shows that a transcriptional regulatory module comprising AP-1 and Schnurri binding sites located upstream of reaper integrate the activities of JNK and Dpp. This arrangement allows JNK to control a migratory behavior without triggering apoptosis. Dpp plays a dual role during dorsal closure. It cooperates with JNK in stimulating cell migration and also prevents JNK from inducing apoptosis.

SUBMITTER: Beira JV

PROVIDER: S-EPMC4220000 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

The Dpp/TGFβ-dependent corepressor Schnurri protects epithelial cells from JNK-induced apoptosis in drosophila embryos.

Beira Jorge V JV Springhorn Alexander A Gunther Stefan S Gunther Stefan S Hufnagel Lars L Pyrowolakis Giorgos G Vincent Jean-Paul JP

Developmental cell 20141009 2

Jun N-terminal kinase (JNK) often mediates apoptosis in response to cellular stress. However, during normal development, JNK signaling controls a variety of live cell behaviors, such as during dorsal closure in Drosophila embryos. During this process, the latent proapoptotic activity of JNK becomes apparent following Dpp signaling suppression, which leads to JNK-dependent transcriptional activation of the proapoptotic gene reaper. Dpp signaling also protects cells from JNK-dependent apoptosis ca ...[more]

PMID: 25307481

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Project description:BackgroundTo identify genes involved in the heart development of Drosophila, we found that embryos lacking raw function exhibited cardial phenotypes. raw was initially identified as a dorsal open group gene. The dorsal open phenotype was demonstrated to be resulted from the aberrant expression of decapentaplegic (dpp), a member of the tumor growth factor beta (TGF-β), signaling pathway. Despite the role of dpp in pattering cardioblasts during early embryogenesis of Drosophila have been demonstrated, how mutation in raw and/or excessive dpp signaling involves in the differentiating heart of Drosophila has not been fully elaborated at late stages.ResultsWe show that raw mutation produced a mild overspecification of cardial cells at stage 14, but these overproduced cells were mostly eliminated in late mutant embryos due to apoptosis. Aberrant dpp signaling is likely to contribute to the cardial phenotype found in raw mutants, because expression of dpp or constitutively activated thickven (tkvCA), the type I receptor of Dpp, induced a raw-like phenotype. Additionally, we show that dpp induced non-autonomous apoptosis through TGFβ activated kinase 1 (TAK1), because mis-expression of a dominant negative form of Drosophila TAK1 (dTAK1DN) was able to suppress cell death in raw mutants or embryos overexpressing dpp. Importantly, we demonstrated that dpp induce its own expression through dTAK1, which also leads to the hyperactivation of Drosophila JNK (DJNK). The hyperactivated DJNK was attributed to be the cause of Dpp/DTAK1-induced apoptosis because overexpression of a dominant negative DJNK, basket (bskDN), suppressed cell death induced by Dpp or DTAK1. Moreover, targeted overexpression of the anti-apoptotic P35 protein, or a dominant negative proapoptotic P53 (P53DN) protein blocked Dpp/DTAK1-induced apoptosis, and rescued heart cells under the raw mutation background.ConclusionsWe find that ectopic Dpp led to DJNK-dependent cardial apoptosis through the non-canonical TGF-β pathway during late embryogenesis of Drosophila. This certainly will increase our understanding of the pathogenesis of cardiomyopathy, because haemodynamic overload can up-regulate TGF-β and death of cardiomyocytes is observed in virtually every myocardial disease. Thus, our study may provide possible medical intervention for human cardiomyopathy.

Dataset Information

The Dpp/TGF?-dependent corepressor Schnurri protects epithelial cells from JNK-induced apoptosis in drosophila embryos.

Publications

The Dpp/TGFβ-dependent corepressor Schnurri protects epithelial cells from JNK-induced apoptosis in drosophila embryos.

Similar Datasets

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