Excessive Dpp signaling induces cardial apoptosis through dTAK1 and dJNK during late embryogenesis of Drosophila

Sheng An Yang, Ming Tsan Su*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

4 引文 斯高帕斯(Scopus)

摘要

Background: To 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. Results: We 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 TGF 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. Conclusions: We 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.

原文英語
文章編號85
期刊Journal of Biomedical Science
18
發行號1
DOIs
出版狀態已發佈 - 2011

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 分子生物學
  • 臨床生物化學
  • 細胞生物學
  • 生物化學(醫學)
  • 藥學(醫學)

指紋

深入研究「Excessive Dpp signaling induces cardial apoptosis through dTAK1 and dJNK during late embryogenesis of Drosophila」主題。共同形成了獨特的指紋。

引用此