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Somatic PI3K activity regulates transition to the spermatocyte stages in Drosophila testis

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Abstract

Spermatogenesis, involving multiple transit amplification divisions and meiosis, occurs within an enclosure formed by two somatic cells. As the cohort of germline cells divide and grow, the surface areas of the somatic cells expand maintaining a tight encapsulation throughout the developmental period. Correlation between the somatic cell growth and germline development is unclear. Here, we report standardization of a quantitative assay developed for estimating the somatic roles of target molecules on germline division and differentiation in Drosophila testis. Using the assay, we studied the somatic roles of phosphatidylinositol-3-kinase (PI3K). It revealed that the expression of PI3KDN is likely to facilitate the early germline development at all stages, and an increase in the somatic PI3K activity during the early stages delays the transition to spermatocyte stage. Together, these results suggest that somatic cell growth plays an important role in regulating the rate of germline development.

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References

  • Ahn S-Y, Kim Y, Kim ST, Swat W and Miner JH 2013 Scaffolding proteins DLG1 and CASK cooperate to maintain the nephron progenitor population during kidney development. J. Am. Soc. Nephrol. 24 1127–1138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biteau B, Hochmuth CE and Jasper H 2011 Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 9 402–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breuhahn K, Longerich T and Schirmacher P 2006 Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 25 3787–3800

    Article  CAS  PubMed  Google Scholar 

  • Cenci G, Bonaccorsi S, Pisano C, Verni F and Gatti M 1994 Chromatin and microtubule organization during premeiotic, meiotic and early postmeiotic stages of Drosophila melanogaster spermatogenesis. J. Cell Sci. 3521–34

  • Chen X, Hiller M, Sancak Y and Fuller MT 2005 Tissue-specific TAFs counteract polycomb to turn on terminal differentiation. Science 310 869–872

    Article  CAS  PubMed  Google Scholar 

  • Chung CY, Potikyan G and Firtel RA 2001 Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol. Cell 7 937–947

    Article  CAS  PubMed  Google Scholar 

  • Corda D, Barretta ML, Cervigni RI and Colanzi A 2012 Golgi complex fragmentation in G2/M transition: an organelle-based cell-cycle checkpoint. IUBMB Life 64 661–670

    Article  CAS  PubMed  Google Scholar 

  • Davies EL and Fuller MT 2008 Regulation of self-renewal and differentiation in adult stem cell lineages: lessons from the drosophila male germ line. Cold Spring Harb. Symp. Quant. Biol. 73 137–145

    Article  CAS  PubMed  Google Scholar 

  • Duan H, Qu L and Shou C 2014 Activation of EGFR-PI3K-AKT signaling is required for Mycoplasma hyorhinis-promoted gastric cancer cell migration. Cancer Cell Int. 14 135

    Article  PubMed  PubMed Central  Google Scholar 

  • Engelman JA, Luo J and Cantley LC 2006 The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 7 606–619

    Article  CAS  PubMed  Google Scholar 

  • Fairchild MJ, Smendziuk CM and Tanentzapf G 2015 A somatic permeability barrier around the germline is essential for Drosophila spermatogenesis. Development 142 268–281

    Article  CAS  PubMed  Google Scholar 

  • Ferreira A and Milán M 2015 Dally proteoglycan mediates the autonomous and nonautonomous effects on tissue growth caused by activation of the PI3K and TOR pathways. PLoS Biol. 13 e1002239

    Article  PubMed  PubMed Central  Google Scholar 

  • Fuller MT 1993 Spermatogenesis. Dev. Drosoph. melanogaster. 1 71–147

    Google Scholar 

  • Fuller MT 1998 Genetic control of cell proliferation and differentiation in Drosophila spermatogenesis. Semin. Cell Dev. Biol. 9 433–444

    Article  CAS  PubMed  Google Scholar 

  • Galagovsky D, Katz MJ, Acevedo JM, Sorianello E, Glavic A and Wappner P 2014 The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner. Mol. Biol. Cell 25 916–924

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao S and Liu Y 2012 Intercepting noncoding messages between germline and soma. Genes Dev. 26 1774–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gönczy P, Matunis E and DiNardo S 1997 bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis. Development 124 4361–4371

    PubMed  Google Scholar 

  • Halfar K, Rommel C, Stocker H and Hafen E 2001 Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development 128 1687–1696

    CAS  PubMed  Google Scholar 

  • Hardy RW, Tokuyasu KT, Lindsley DL and Garavito M 1979 The germinal proliferation center in the testis of Drosophila melanogaster. J. Ultrastruct. Res. 69 180–190

    Article  CAS  PubMed  Google Scholar 

  • Hudson AG, Parrott BB, Qian Y and Schulz C 2013 A temporal signature of epidermal growth factor signaling regulates the differentiation of germline cells in testes of Drosophila melanogaster. PLoS One 8 e70678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ibar C, Cataldo VF, Vásquez-Doorman C, Olguín P and Glavic A 2013 Drosophila p53-related protein kinase is required for PI3K/TOR pathway-dependent growth. Development 140 1282–1291

    Article  CAS  PubMed  Google Scholar 

  • Insco ML, Leon A, Tam CH, McKearin DM and Fuller MT 2009 Accumulation of a differentiation regulator specifies transit amplifying division number in an adult stem cell lineage. Proc. Natl. Acad. Sci. USA 106 22311–22316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joti P, Ghosh-Roy A and Ray K 2011 Dynein light chain 1 functions in somatic cyst cells regulate spermatogonial divisions in Drosophila. Sci. Rep. 1 173

    Article  PubMed  PubMed Central  Google Scholar 

  • Karim FD and Rubin GM 1998 Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues. Development 125 1–9

    CAS  PubMed  Google Scholar 

  • Kasahara K, Goto H, Izawa I, Kiyono T, Watanabe N, Elowe S, Nigg EA and Inagaki M 2013 PI 3-kinase-dependent phosphorylation of Plk1-Ser99 promotes association with 14-3-3γ and is required for metaphase-anaphase transition. Nat. Commun. 4 1882

    Article  PubMed  PubMed Central  Google Scholar 

  • Kiger AA, White-Cooper H and Fuller MT 2000 Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature 407 750–754

    Article  CAS  PubMed  Google Scholar 

  • Kumar M, Kong K and Javier RT 2014 Hijacking Dlg1 for oncogenic phosphatidylinositol 3-kinase activation in human epithelial cells is a conserved mechanism of human adenovirus E4-ORF1 proteins. J. Virol. 88 14268–14277

    Article  PubMed  PubMed Central  Google Scholar 

  • Kusumi N, Watanabe M, Yamada H, Li S-A, Kashiwakura Y, Matsukawa T, Nagai A, Nasu Y, et al. 2007 Implication of amphiphysin 1 and dynamin 2 in tubulobulbar complex formation and spermatid release. Cell Struct. Funct. 32 101–113

    Article  CAS  PubMed  Google Scholar 

  • Lee J-O, Yang H, Georgescu M-M, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, et al. 1999 Crystal structure of the PTEN tumor suppressor. Cell 99 323–334

    Article  CAS  PubMed  Google Scholar 

  • Leevers SJ, Weinkove D, MacDougall LK, Hafen E and Waterfield MD 1996 The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J. 15 6584–6594

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li MA, Alls JD, Avancini RM, Koo K and Godt D 2003 The large Maf factor traffic jam controls gonad morphogenesis in Drosophila. Nat. Cell Biol. 5 994–1000

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Minor NT, Park JK, McKearin DM and Maines JZ 2009 Bam and Bgcn antagonize Nanos-dependent germ-line stem cell maintenance. Proc. Natl. Acad. Sci. USA 106 9304–9309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim JGY and Fuller MT 2012 Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes. Proc. Natl. Acad. Sci. USA 109 18477–18481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin TY, Viswanathan S, Wood C, Wilson PG, Wolf N and Fuller MT 1996 Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males. Development 122 1331–1341

    CAS  PubMed  Google Scholar 

  • Lindsley DT and Tokuyasu KT 1980 Spermatogenesis. In: Ashburner M, Wright TRF (eds) The Genetics and Biology of Drosophila, Vol. 2d. 225–294

  • McKee BD, Yan R and Tsai J-H 2012 Meiosis in male Drosophila. Spermatogenesis 2 167–184

    Article  PubMed  PubMed Central  Google Scholar 

  • Murga C, Laguinge L, Wetzker R, Cuadrado A and Gutkind JS 1998 Activation of Akt/protein kinase B by G protein-coupled receptors: a role for and subunits of heterotrimeric g proteins acting through phosphatidylinositol-3-OH kinase. J. Biol. Chem. 273 19080–19085

    Article  CAS  PubMed  Google Scholar 

  • Ohlstein B and McKearin D 1997 Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells. Development 124 3651–3662

    CAS  PubMed  Google Scholar 

  • Papagiannouli F and Mechler BM 2009 discs large regulates somatic cyst cell survival and expansion in Drosophila testis. Cell Res. 19 1139–1149

    Article  PubMed  Google Scholar 

  • Payne C and Schatten G 2003 Golgi dynamics during meiosis are distinct from mitosis and are coupled to endoplasmic reticulum dynamics until fertilization. Dev. Biol. 264 50–63

    Article  CAS  PubMed  Google Scholar 

  • Read RD, Cavenee WK, Furnari FB and Thomas JB 2009 A drosophila model for EGFR-Ras and PI3K-dependent human glioma. PLoS Genet. 5 e1000374

    Article  PubMed  PubMed Central  Google Scholar 

  • Salony S, Alves X, Dey-Guha CP, Ritsma I, Boukhali L, Lee M, Chowdhury JH, Ross J, et al. 2016 AKT inhibition promotes nonautonomous cancer cell survival. Mol. Cancer Ther. 15 142–153

    Article  CAS  PubMed  Google Scholar 

  • Schulz C, Kiger AA, Tazuke SI, Yamashita YM, Pantalena-Filho LC, Jones DL, Wood CG and Fuller MT 2004 A misexpression screen reveals effects of bag-of-marbles and TGF beta class signaling on the Drosophila male germ-line stem cell lineage. Genetics 167 707–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soler A, Angulo-Urarte A and Graupera M 2015 PI3K at the crossroads of tumor angiogenesis signaling pathways. Mol. Cell. Oncol. 2 e975624

    Article  PubMed  PubMed Central  Google Scholar 

  • Tartakoff AM and Vassalli P 1983 Lectin-binding sites as markers of Golgi subcompartments: proximal-to-distal maturation of oligosaccharides. J. Cell Biol. 97 1243–1248

    Article  CAS  PubMed  Google Scholar 

  • Tétreault M-P, Chailler P, Beaulieu J-F, Rivard N and Ménard D 2008 Epidermal growth factor receptor-dependent PI3K-activation promotes restitution of wounded human gastric epithelial monolayers. J. Cell. Physiol. 214 545–557

    Article  PubMed  Google Scholar 

  • Toulany M, Baumann M and Rodemann HP 2007 Stimulated PI3K-AKT signaling mediated through ligand or radiation-induced EGFR depends indirectly, but not directly, on constitutive K-Ras activity. Mol. Cancer Res. 5 863–872

    Article  CAS  PubMed  Google Scholar 

  • Tran J, Brenner TJ and DiNardo S 2000 Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 407 754–757

    Article  CAS  PubMed  Google Scholar 

  • Wei J-H and Seemann J 2010 Unraveling the Golgi ribbon. Traffic 11 1391–1400

    Article  PubMed  PubMed Central  Google Scholar 

  • Weinkove D, Neufeld TP, Twardzik T, Waterfield MD and Leevers SJ 1999 Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr. Biol. 9 1019–1029

    Article  CAS  PubMed  Google Scholar 

  • White-Cooper H, Schafer MA, Alphey LS and Fuller MT 1998 Transcriptional and post-transcriptional control mechanisms coordinate the onset of spermatid differentiation with meiosis I in Drosophila. Development. 125 125–134

    CAS  PubMed  Google Scholar 

  • Whites MF and Kahn CR 1994 The insulin signaling system*. J. Biol. Chem. 269 1–4

    Google Scholar 

  • Wu MY and Hill CS 2009 TGF-β superfamily signaling in embryonic development and homeostasis. Dev. Cell. 16 329–343

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Hepner K, Castelino-Prabhu S, Do D, Kaye MB, Yuan XJ, Wood J, Ross C, et al. 2000a Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc. Natl. Acad. Sci. USA 97 4233–4238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q and Lasky LA 2000b Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J. Biol. Chem. 275 21477–21485

  • Xi X, Tatei K, Kihara Y and Izumi T 2014 Expression pattern of class I phosphoinositide 3-kinase and distribution of its product, phosphatidylinositol-3,4,5-trisphosphate, during Drosophila embryogenesis. Gene Expr. Patterns 15 88–95

    Article  CAS  PubMed  Google Scholar 

  • Zoller R and Schulz C 2012 The Drosophila cyst stem cell lineage. Spermatogenesis 2 145–157

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Kenneth Irvine, Dorothea Godt, the Bloomington Stock Center, Vienna Drosophila Resource Center, and Developmental Studies Hybridoma Bank, Iowa, USA, for the fly stocks and other reagents. We also acknowledge Prakash Joti for experimental support. The project is supported by an intramural fund of TIFR, Department of Atomic Energy, and by the DBT Grant BT/PR/4585/Med/31/155/2012 Dtd. 28/09/2012.

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  1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, 400 005, India

    Samir Gupta & Krishanu Ray

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  1. Samir Gupta
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  2. Krishanu Ray
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Correspondence to Krishanu Ray.

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[Gupta S and Ray K 2017 Somatic PI3K activity regulates transition to the spermatocyte stages in Drosophila testis. J. Biosci.]

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Gupta, S., Ray, K. Somatic PI3K activity regulates transition to the spermatocyte stages in Drosophila testis. J Biosci 42, 285–297 (2017). https://doi.org/10.1007/s12038-017-9678-5

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