Drosophila jumu modulates apoptosis via a JNK-dependent pathway and is required for other processes in wing development
Previous studies in several model organisms have revealed that members of the Forkhead (Fkh) transcription factor family have multiple functions. Drosophila Jumeau (Jumu), a member of this family, participates in cardiogenesis, hematopoiesis and immune system homeostasis. Here, we show that loss of jumu function positively regulates or triggers apoptosis via a JNK-dependent pathway in wing development. jumu mutants showed reduced wing size and increased apoptosis. Moreover, we observed a loss of the anterior cross vein (ACV) phenotype that was similar to that observed in wings in which JNK signaling has been ectopically activated. The JNK signaling markers puckered (puc) and p-JNK were also significantly increased in the wing discs of jumu mutants. In addition, apoptosis induced by the loss of jumu was rescued by knocking down JNK, indicating a role for JNK in reducing jumu-induced apoptosis. Jumu could also control wing margin development via the positive regulation of cut expression, and the observed wing margin defect did not result from a loss of jumu-induced apoptosis. Further, jumu deficiency in the pupal wing could induce multiple wing hairs via a Rho1-mediated planar cell polarity pathway, but abnormal Rho1 expression was not why jumu loss induced apoptosis via a JNK-dependent pathway in wing discs.
KeywordsJumu Apoptosis JNK pathway Wing development
We thank Alan M Michelson for supplying us with the fly strains used in this study. We gratefully acknowledge Vienna Drosophila RNAi Stock Center, Tsinghua Drosophila model animal center, GenExel Stock Center and Developmental Studies Hybridoma Bank for providing fly lines and antibodies.
XCW, investigation, visualization, writing—original draft; LZ, review; LHJ, supervision, funding acquisition, project administration—review and editing.
This work was supported by the National Natural Science Foundation of China (31772521) and Fundamental Research Funds for the Central Universities (2572018CG05, 2572015AA10).
Compliance with ethical standards
The authors declare no competing or financial interests.
- 6.Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S, Bang SM, Jeong Y, Chung WJ, Lee IS, Jeong G, Chung J, Cho KS (2013) Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet 9:e1003412. https://doi.org/10.1371/journal.pgen.1003412 CrossRefGoogle Scholar
- 8.Umemori M, Habara O, Iwata T, Maeda K, Nishinoue K, Okabe A, Takemura M, Takahashi K, Saigo K, Ueda R, Adachi-Yamada T (2009) RNAi-mediated knockdown showing impaired cell survival in Drosophila wing imaginal disc. Gene Regul Syst Bio 3:11–20Google Scholar
- 9.Dichtel-Danjoy ML, Ma D, Dourlen P, Chatelain G, Napoletano F, Robin M, Corbet M, Levet C, Hafsi H, Hainaut P, Ryoo HD, Bourdon JC, Mollereau B (2013) Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. Cell Death Differ 20:108–116. https://doi.org/10.1038/cdd.2012.100 CrossRefGoogle Scholar
- 11.Fan Y, Wang S, Hernandez J, Yenigun VB, Hertlein G, Fogarty CE, Lindblad JL, Bergmann A (2014) Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila. PLoS Genet 10:e1004131. https://doi.org/10.1371/journal.pgen.1004131 CrossRefGoogle Scholar
- 15.Cheah PY, Chia W, Yang X (2000) Jumeaux, a novel Drosophila winged-helix family protein, is required for generating asymmetric sibling neuronal cell fates. Development 127:3325–3335Google Scholar
- 17.Ahmad SM, Tansey TR, Busser BW, Nolte MT, Jeffries N, Gisselbrecht SS, Rusan NM, Michelson AM (2012) Two forkhead transcription factors regulate the division of cardiac progenitor cells by a polo-dependent pathway. Dev Cell 23:97–111. https://doi.org/10.1016/j.devcel.2012.05.011 CrossRefGoogle Scholar
- 18.Ahmad SM, Bhattacharyya P, Jeffries N, Gisselbrecht SS, Michelson AM (2016) Two Forkhead transcription factors regulate cardiac progenitor specification by controlling the expression of receptors of the fibroblast growth factor and Wnt signaling pathways. Development 143:306–317. https://doi.org/10.1242/dev CrossRefGoogle Scholar
- 21.Hao Y, Jin LH (2017) Dual role for Jumu in the control of hematopoietic progenitors in the Drosophila lymph gland. Elife 6. pii: e25094. https://doi.org/10.7554/eLife.25094
- 22.Zhu X, Ahmad SM, Aboukhalil A, Busser BW, Kim Y, Tansey TR, Haimovich A, Jeffries N, Bulyk ML, Michelson AM (2012) Differential regulation of mesodermal gene expression by Drosophila cell type-specific forkhead transcription factors. Development 139:1457–1466. https://doi.org/10.1242/dev.069005 CrossRefGoogle Scholar
- 26.Guillén I, Mullor JL, Capdevila J, Sánchez-Herrero E, Morata G, Guerrero I (1995) The function of engrailed and the specification of Drosophila wing pattern. Development 121:3447–3456Google Scholar
- 27.Liu Z, Matsuoka S, Enoki A, Yamamoto T, Furukawa K, Yamasaki Y, Nishida Y, Sugiyama S (2011) Negative modulation of bone morphogenetic protein signaling by Dullard during wing vein formation in Drosophila. Dev Growth Differ 53:822–841. https://doi.org/10.1111/j.1440-169X.2011.01289.x CrossRefGoogle Scholar
- 30.Hay BA, Wolff T, Rubin GM (1994) Expression of baculovirus P35 prevents cell death in Drosophila. Development 120:2121–2129Google Scholar
- 42.Martín-Castellanos C, Edgar BA (2002) A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development 129:1003–1013Google Scholar
- 46.Neumann CJ, Cohen SM (1997) Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development 124:871–880Google Scholar
- 55.Bloor JW, Kiehart DP (2002) Drosophila RhoA regulates the cytoskeleton and cell-cell adhesion in the developing epidermis. Development 129:3173–3183Google Scholar
- 59.Magie CR, Pinto-Santini D, Parkhurst SM (2002) Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. Development 129:3771–3782Google Scholar