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Twinstar/cofilin is required for regulation of epithelial integrity and tissue growth in Drosophila

Oncogene volume 35, pages 5144–5154 (2016)Cite this article

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Abstract

Regulation of actin assembly and depolymerization is important for the organization of epithelia. Recent studies have shown that the actin-capping proteins are required to prevent cell extrusion and inappropriate activation of Yorkie (Yki) activity in Drosophila, implicating the importance of actin regulation for epithelial integrity and Yki-dependent tissue growth. However, the role of Twinstar (Tsr), the Drosophila homolog for cofilin/actin depolymerization factor (ADF), in epithelial integrity and Hippo signaling is unknown. Here we demonstrate that reduction of Tsr by RNA interference (RNAi) or mutant clones in wing imaginal disc induces not only F-actin accumulation but also ectopic expression of Wingless (Wg) and Yki target gene expanded (ex). Knockdown of Yki in Tsr-depleted cells reduced the level of ectopic Wg expression. Reduced Tsr also led to downregulation of cell junction proteins and extrusion of affected cells from the basal part of the epithelium. Rho GTPase 1 was upregulated in Tsr-depleted tissue, supporting the Tsr function in the inhibition of cell extrusion from the epithelium. Tsr is also required for blocking cell death and c-Jun N-terminal kinase (JNK) signaling. Ectopic JNK activation induced caspase activation but did not cause cell extrusion. Further, the invasiveness of Tsr-depleted cells was not suppressed by inhibition of cell death or JNK signaling. In contrast, Yki upregulation was significantly suppressed by cell death inhibition. Taken together, our data suggest that Tsr is required for cell survival and tissue growth by regulating JNK and Yki signaling while maintaining the epithelial integrity by controlling cell junctions. This study provides an insight into potential roles of ADF/cofilin in invasive cell migration and tumor suppression in higher animals.

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Acknowledgements

We are grateful to Drs David Helfman and Kyung-Ok Cho for critical comments on the manuscript. We thank Drs Florence Janody, Jongkyeong Chung and Kenneth Irvine for providing flies and antibodies mentioned in the text. We acknowledge the Bloomington Drosophila Stock Center, DGGC, the NIG-Fly Stock Center and the Developmental Studies Hybridoma Bank for fly stocks and antibodies. We thank the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing transgenic RNAi fly stocks. This research was supported by a National Research Laboratory Grant (NRF-2011-0028326) and a Global Research Laboratory Grant (2014K1A1A2042982) through the National Research Foundation of Korea, funded by the Korean, Ministry of Education, Science and Technology.

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  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon, Korea

    C Ko, Y-G Kim, T P Le & K-W Choi

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Correspondence to K-W Choi.

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Ko, C., Kim, YG., Le, T. et al. Twinstar/cofilin is required for regulation of epithelial integrity and tissue growth in Drosophila. Oncogene 35, 5144–5154 (2016). https://doi.org/10.1038/onc.2016.46

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