The lack of autophagy triggers precocious activation of Notch signaling during Drosophila oogenesis

BMC Developmental Biology

Katja Köhler¹  Ernst Hafen¹  Julia MI Barth¹ 

[1] Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland

关键词: Notch;    Oogenesis;    Follicle cells;    Drosophila;    Autophagy;   

Others  :  1086331
DOI  :  10.1186/1471-213X-12-35

 received in 2012-07-26, accepted in 2012-11-30,  发布年份 2012

【 摘 要 】

Background

The proper balance of autophagy, a lysosome-mediated degradation process, is indispensable for oogenesis in Drosophila. We recently demonstrated that egg development depends on autophagy in the somatic follicle cells (FC), but not in the germline cells (GCs). However, the lack of autophagy only affects oogenesis when FCs are autophagy-deficient but GCs are wild type, indicating that a dysfunctional signaling between soma and germline may be responsible for the oogenesis defects. Thus, autophagy could play an essential role in modulating signal transduction pathways during egg development.

Results

Here, we provide further evidence for the necessity of autophagy during oogenesis and demonstrate that autophagy is especially required in subsets of FCs. Generation of autophagy-deficient FCs leads to a wide range of phenotypes that are similar to mutants with defects in the classical cell-cell signaling pathways in the ovary. Interestingly, we observe that loss of autophagy leads to a precocious activation of the Notch pathway in the FCs as monitored by the expression of Cut and Hindsight, two downstream effectors of Notch signaling.

Conclusion

Our findings point to an unexpected function for autophagy in the modulation of the Notch signaling pathway during Drosophila oogenesis and suggest a function for autophagy in proper receptor activation. Egg development is affected by an imbalance of autophagy between signal sending (germline) and signal receiving cell (FC), thus the lack of autophagy in the germline is likely to decrease the amount of active ligand and accordingly compensates for increased signaling in autophagy-defective follicle cells.

【 授权许可】

   
2012 Barth et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Chen Y, Klionsky DJ: The regulation of autophagy - unanswered questions. J Cell Sci 2011, 124:161-170.
• [2]Barth JMI, Szabad J, Hafen E, Köhler K: Autophagy in Drosophila ovaries is induced by starvation and is required for oogenesis. Cell Death Differ 2011, 18(6):915-924.
• [3]Berry D, Baehrecke E: Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 2007, 131:1137-1148.
• [4]Rusten T, Lindmo K, Juhasz G, Sass M, Seglen P, Brech A, Stenmark H: Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway. Dev Cell 2004, 7:179-192.
• [5]Scott R, Schuldiner O, Neufeld T: Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell 2004, 7:167-178.
• [6]Drummond-Barbosa D, Spradling A: Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev Biol 2001, 231:265-278.
• [7]Hou Y, Chittaranjan S, Barbosa S, McCall K, Gorski S: Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis. J Cell Biol 2008, 182:1127-1139.
• [8]Nezis I, Lamark T, Velentzas A, Rusten T, Bjorkoy G, Johansen T, Papassideri I, Stravopodis D, Margaritis L, Stenmark H, et al.: Cell death during Drosophila melanogaster early oogenesis is mediated through autophagy. Autophagy 2009, 5:298-302.
• [9]Peterson J, Barkett M, McCall K: Stage-specific regulation of caspase activity in drosophila oogenesis. Dev Biol 2003, 260:113-123.
• [10]Velentzas AD, Nezis IP, Stravopodis DJ, Papassideri IS, Margaritis LH: Mechanisms of programmed cell death during oogenesis in Drosophila virilis. Cell Tissue Res 2007, 327:399-414.
• [11]Nezis I, Stravopodis D, Margaritis L, Papassideri I: Programmed cell death of follicular epithelium during the late developmental stages of oogenesis in the fruit flies Bactrocera oleae and Ceratitis capitata (Diptera, Tephritidae) is mediated by autophagy. Dev Growth Differ 2006, 48:189-198.
• [12]Nezis IP, Shravage BV, Sagona AP, Lamark T, Bjorkoy G, Johansen T, Rusten TE, Brech A, Baehrecke EH, Stenmark H: Autophagic degradation of dBruce controls DNA fragmentation in nurse cells during late Drosophila melanogaster oogenesis. J Cell Biol 2010, 190:523-531.
• [13]Poulton J, Deng W: Cell-cell communication and axis specification in the Drosophila oocyte. Dev Biol 2007, 311:1-10.
• [14]González-Reyes A, Elliott H, Johnston D: Polarization of both major body axes in Drosophila by gurken-torpedo signalling. Nature 1995, 375:654-658.
• [15]Chang YY, Neufeld TP: Autophagy takes flight in Drosophila. FEBS Lett 2010, 584:1342-1349.
• [16]Assa-Kunik E, Torres IL, Schejter ED, Johnston DS, Shilo B-Z: Drosophila follicle cells are patterned by multiple levels of Notch signaling and antagonism between the Notch and JAK/STAT pathways. Development 2007, 134:1161-1169.
• [17]López-Schier H, Johnston D: Delta signaling from the germ line controls the proliferation and differentiation of the somatic follicle cells during Drosophila oogenesis. Genes Dev 2001, 15:1393.
• [18]Ward E, Zhou X, Riddiford L, Berg C, Ruohola-Baker H: Border of Notch activity establishes a boundary between the two dorsal appendage tube cell types. Dev Biol 2006, 297:461-470.
• [19]Avraham R, Yarden Y: Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nat Rev Mol Cell Biol 2011, 12:104-117.
• [20]Yamamoto S, Charng W-L, Bellen HJ: Endocytosis and Intracellular Trafficking of Notch and Its Ligands. 92nd edition. 2010.
• [21]Berg C: The Drosophila shell game: patterning genes and morphological change. Trends Genet 2005, 21:346-355.
• [22]Giorgi F, Deri P: Cell death in ovarian chambers of Drosophila melanogaster. J Embryol Exp Morphol 1976, 35:521-533.
• [23]Nezis IP, Stravopodis DJ, Papassideri I, Robert-Nicoud M, Margaritis LH: Stage-specific apoptotic patterns during Drosophila oogenesis. Eur J Cell Biol 2000, 79:610-620.
• [24]Brand A, Perrimon N: Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993, 118:401-415.
• [25]Duffy JB, Harrison DA, Perrimon N: Identifying loci required for follicular patterning using directed mosaics. Development 1998, 125:2263-2271.
• [26]Montell DJ: Border-cell migration: the race is on. Nat Rev Mol Cell Biol 2003, 4:13-24.
• [27]Rorth P, Szabo K, Bailey A, Laverty T, Rehm J, Rubin GM, Weigmann K, Milan M, Benes V, Ansorge W, et al.: Systematic gain-of-function genetics in Drosophila. Development 1998, 125:1049-1057.
• [28]Manseau L, Baradaran A, Brower D, Budhu A, Elefant F, Phan H, Philp AV, Yang M, Glover D, Kaiser K, et al.: GAL4 enhancer traps expressed in the embryo, larval brain, imaginal discs, and ovary of Drosophila. Dev Dyn 1997, 209:310-322.
• [29]Hartman TR, Zinshteyn D, Schofield HK, Nicolas E, Okada A, O’Reilly AM: Drosophila Boi limits Hedgehog levels to suppress follicle stem cell proliferation. J Cell Biol 2010, 191:943-952.
• [30]Bai J, Montell D: Eyes absent, a key repressor of polar cell fate during Drosophila oogenesis. Development 2002, 129:5377-5388.
• [31]Ito K, Awano W, Suzuki K, Hiromi Y, Yamamoto D: The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells (vol 124, pg 761, 1997). Development 1997, 124:U2-U2.
• [32]Roth S, Lynch JA: Symmetry breaking during Drosophila oogenesis. Cold Spring Harbor Perspect Biol 2009, 1:a001891.
• [33]Xi R, McGregor JR, Harrison DA: A gradient of JAK pathway activity patterns the anterior-posterior axis of the follicular epithelium. Dev Cell 2003, 4:167-177.
• [34]Deng WM, Bownes M: Patterning and morphogenesis of the follicle cell epithelium during Drosophila oogenesis. Int J Dev Biol 1998, 42:541-552.
• [35]Sun J, Deng W-M: Notch-dependent downregulation of the homeodomain gene cut is required for the mitotic cycle/endocycle switch and cell differentiation in Drosophila follicle cells. Development 2005, 132:4299-4308.
• [36]Sun J, Deng W-M: Hindsight mediates the role of notch in suppressing hedgehog signaling and cell proliferation. Dev Cell 2007, 12:431-442.
• [37]Xu T, Caron LA, Fehon RG, Artavanis-Tsakonas S: The involvement of the Notch locus in Drosophila oogenesis. Development 1992, 115:913-922.
• [38]Zhao D, Clyde D, Bownes M: Expression of fringe is down regulated by gurken/epidermal growth factor receptor signalling and Is required for the morphogenesis of ovarian follicle cells. J Cell Sci 2000, 113(Pt 21):3781-3794.
• [39]Ranganathan P, Weaver KL, Capobianco AJ: Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer 2011, 11:338-351.
• [40]Goode S, Morgan M, Liang YP, Mahowald AP: Brainiac encodes a novel, putative secreted protein that cooperates with Grk TGF alpha in the genesis of the follicular epithelium. Dev Biol 1996, 178:35-50.
• [41]McGregor JR, Xi R, Harrison DA: JAK signaling is somatically required for follicle cell differentiation in Drosophila. Development 2002, 129:705.
• [42]Thumm M, Kadowaki T: The loss of Drosophila APG4/AUT2 function modifies the phenotypes of cut and Notch signaling pathway mutants. Mol Genet Genomics 2001, 266:657-663.
• [43]Vaccari T, Lu H, Kanwar R, Fortini ME, Bilder D: Endosomal entry regulates Notch receptor activation in Drosophila melanogaster. J Cell Biol 2008, 180:755-762.
• [44]Lee G, Liang C, Park G, Jang C, Jung JU, Chung J: UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila. Dev Biol 2011, 356:588-597.
• [45]Juhasz G, Hill JH, Yan Y, Sass M, Baehrecke EH, Backer JM, Neufeld TP: The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol 2008, 181:655-666.
• [46]Rusten TE, Vaccari T, Lindmo K, Rodahl LMW, Nezis IP, Sem-Jacobsen C, Wendler F, Vincent J-P, Brech A, Bilder D, et al.: ESCRTs and Fab1 regulate distinct steps of autophagy. Curr Biol 2007, 17:1817-1825.
• [47]Gordon PB, Seglen PO: Prelysosomal convergence of autophagic and endocytic pathways. Biochem Biophys Res Commun 1988, 151:40-47.
• [48]Liou W, Geuze HJ, Geelen MJ, Slot JW: The autophagic and endocytic pathways converge at the nascent autophagic vacuoles. J Cell Biol 1997, 136:61-70.
• [49]Larkin MK, Holder K, Yost C, Giniger E, Ruohola-Baker H: Expression of constitutively active Notch arrests follicle cells at a precursor stage during Drosophila oogenesis and disrupts the anterior-posterior axis of the oocyte. Development 1996, 122:3639.
• [50]Sorkin A, Goh LK: Endocytosis and intracellular trafficking of ErbBs. Exp Cell Res 2009, 315:683-696.
• [51]Kirkin V, McEwan DG, Novak I, Dikic I: A role for ubiquitin in selective autophagy. Mol Cell 2009, 34:259-269.
• [52]Gao C, Cao W, Bao L, Zuo W, Xie G, Cai T, Fu W, Zhang J, Wu W, Zhang X, et al.: Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation. Nat Cell Biol 2010, 12:781-790.
• [53]Muzzopappa M, Wappner P: Multiple roles of the F-box protein Slimb in Drosophila egg chamber development. Development 2005, 132:2561-2571.
• [54]Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama KI: Fbxw7-dependent degradation of Notch is required for control of “stemness” and neuronal-glial differentiation in neural stem cells. J Biol Chem 2011, 286:13754-13764.
• [55]Sandilands E, Serrels B, McEwan DG, Morton JP, Macagno JP, McLeod K, Stevens C, Brunton VG, Langdon WY, Vidal M, et al.: Autophagic targeting of Src promotes cancer cell survival following reduced FAK signalling. Nat Cell Biol 2011, 14:51-60.
• [56]Wang Y, Chen Z, Bergmann A: Regulation of EGFR and Notch signaling by distinct isoforms of D-cbl during Drosophila development. Dev Biol 2010, 342:1-10.
• [57]Schweisguth F: Regulation of notch signaling activity. Curr Biol 2004, 14:R129-R138.
• [58]Nichols JT, Miyamoto A, Weinmaster G: Notch signaling–constantly on the move. Traffic 2007, 8:959-969.
• [59]Parks AL, Klueg KM, Stout JR, Muskavitch MA: Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development 2000, 127:1373-1385.
• [60]Chitnis A: Why is delta endocytosis required for effective activation of notch? Dev Dyn 2006, 235:886-894.
• [61]Csikos G, Lippai M, Lukacsovich T, Juhasz G, Henn L, Erdelyi M, Maroy P, Sass M: A novel role for the Drosophila epsin (lqf): involvement in autophagy. Autophagy 2009, 5:636-648.
• [62]Overstreet E, Chen X, Wendland B, Fischer JA: Either part of a Drosophila epsin protein, divided after the ENTH domain, functions in endocytosis of delta in the developing eye. Curr Biol 2003, 13:854-860.
• [63]Chang Y, Juhasz G, Goraksha-Hicks P, Arsham A, Mallin D, Muller L, Neufeld T: Nutrient-dependent regulation of autophagy through the target of rapamycin pathway. Biochem Soc Trans 2009, 37:232-236.
• [64]Kawahashi K, Hayashi S: Dynamic intracellular distribution of Notch during activation and asymmetric cell division revealed by functional fluorescent fusion proteins. Genes Cells 2010, 15:749-759.
• [65]Pai LM, Barcelo G, Schupbach T: D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis. Cell 2000, 103:51-61.
• [66]Schupbach T, Roth S: Dorsoventral patterning in Drosophila oogenesis. Curr Opin Genet Dev 1994, 4:502-507.
• [67]Britton JS, Lockwood WK, Li L, Cohen SM, Edgar BA: Drosophila’s insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell 2002, 2:239-249.