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Soma–germline interactions coordinate homeostasis and growth in the Drosophila gonad

Abstract

The ability of organs such as the liver or the lymphoid system to maintain their original size or regain it after injury is well documented1,2. However, little is known about how these organs sense that equilibrium is breached, and how they cease changing when homeostasis is reached. Similarly, it remains unclear how, during normal development, different cell types within an organ coordinate their growth. Here we show that during gonad development in the fruitfly Drosophila melanogaster the proliferation of primordial germ cells (PGCs) and survival of the somatic intermingled cells (ICs) that contact them are coordinated by means of a feedback mechanism composed of a positive signal and a negative signal. PGCs express the EGF receptor (EGFR) ligand Spitz, which is required for IC survival. In turn, ICs inhibit PGC proliferation. Thus, homeostasis and coordination of growth between soma and germ line in the larval ovary is achieved by using a sensor of PGC numbers (EGFR-mediated survival of ICs) coupled to a correction mechanism inhibiting PGC proliferation. This feedback loop ensures that sufficient numbers of PGCs exist to fill all the stem-cell niches that form at the end of larval development. We propose that similar feedback mechanisms might be generally used for coordinated growth, regeneration and homeostasis.

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Figure 1: The division of PGCs in the larval ovary is regulated.
Figure 2: Abrogation of somatic EGFR signalling causes PGC overproliferation.
Figure 3: Death of IC causes PGC overproliferation.
Figure 4: PGCs determine intermingled cell number.

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References

  1. Freitas, A. A. & Rocha, B. Population biology of lymphocytes: the flight for survival. Annu. Rev. Immunol. 18, 83–111 (2000)

    Article  CAS  PubMed  Google Scholar 

  2. Michalopoulos, G. K. & DeFrances, M. C. Liver regeneration. Science 276, 60–66 (1997)

    Article  CAS  PubMed  Google Scholar 

  3. Gilboa, L. & Lehmann, R. How different is Venus from Mars? The genetics of germ-line stem cells in Drosophila females and males. Development 131, 4895–4905 (2004)

    Article  CAS  PubMed  Google Scholar 

  4. Godt, D. & Laski, F. A. Mechanisms of cell rearrangement and cell recruitment in Drosophila ovary morphogenesis and the requirement of bric a brac. Development 121, 173–187 (1995)

    CAS  PubMed  Google Scholar 

  5. Song, X., Zhu, C. H., Doan, C. & Xie, T. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 296, 1855–1857 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Zhu, C. H. & Xie, T. Clonal expansion of ovarian germline stem cells during niche formation in Drosophila. Development 130, 2579–2588 (2003)

    Article  CAS  PubMed  Google Scholar 

  7. Poirié, M., Niederer, E. & Steinmann-Zwicky, M. A sex-specific number of germ cells in embryonic gonads of Drosophila. Development 121, 1867–1873 (1995)

    PubMed  Google Scholar 

  8. Robertson, S. E., Dockendorff, T. C., Leatherman, J. L., Faulkner, D. L. & Jongens, T. A. germ cell-less is required only during the establishment of the germ cell lineage of Drosophila and has activities which are dependent and independent of its localization to the nuclear envelope. Dev. Biol. 215, 288–297 (1999)

    Article  CAS  PubMed  Google Scholar 

  9. Yohn, C. B., Pusateri, L., Barbosa, V. & Lehmann, R. l(3)malignant brain tumor and three novel genes are required for Drosophila germ-cell formation. Genetics 165, 1889–1900 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Van Doren, M., Williamson, A. & Lehmann, R. Regulation of zygotic gene expression in Drosophila primordial germ cells. Curr. Biol. 8, 243–246 (1998)

    Article  CAS  PubMed  Google Scholar 

  11. Shilo, B. Z. Signaling by the Drosophila epidermal growth factor receptor pathway during development. Exp. Cell Res. 284, 140–149 (2003)

    Article  CAS  PubMed  Google Scholar 

  12. Nilson, L. A. & Schupbach, T. EGF receptor signaling in Drosophila oogenesis. Curr. Top. Dev. Biol. 44, 203–243 (1999)

    Article  CAS  PubMed  Google Scholar 

  13. Schulz, C., Wood, C. G., Jones, D. L., Tazuke, S. I. & Fuller, M. T. Signaling from germ cells mediated by the rhomboid homolog stet organizes encapsulation by somatic support cells. Development 129, 4523–4534 (2002)

    CAS  PubMed  Google Scholar 

  14. Li, M. A., Alls, J. D., Avancini, R. M., Koo, K. & Godt, D. The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila. Nature Cell Biol. 5, 994–1000 (2003)

    Article  CAS  PubMed  Google Scholar 

  15. Bergmann, A., Tugentman, M., Shilo, B. Z. & Steller, H. Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for trophic survival signaling. Dev. Cell 2, 159–170 (2002)

    Article  CAS  PubMed  Google Scholar 

  16. Datar, S. A., Jacobs, H. W., de la Cruz, A. F., Lehner, C. F. & Edgar, B. A. The Drosophila cyclin D-Cdk4 complex promotes cellular growth. EMBO J. 19, 4543–4554 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kai, T. & Spradling, A. An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc. Natl Acad. Sci. USA 100, 4633–4638 (2003)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Margolis, J. & Spradling, A. Identification and behavior of epithelial stem cells in the Drosophila ovary. Development 121, 3797–3807 (1995)

    CAS  PubMed  Google Scholar 

  19. Van Buskirk, C. & Schupbach, T. Versatility in signalling: multiple responses to EGF receptor activation during Drosophila oogenesis. Trends Cell Biol. 9, 1–4 (1999)

    Article  CAS  PubMed  Google Scholar 

  20. Tran, J., Brenner, T. J. & DiNardo, S. Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 407, 754–757 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Kiger, A. A., White-Cooper, H. & Fuller, M. T. Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature 407, 750–754 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Roth, S., Neumann-Silberberg, F. S., Barcelo, G. & Schüpbach, T. cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila. Cell 81, 967–978 (1995)

    Article  CAS  PubMed  Google Scholar 

  23. Gilboa, L. & Lehmann, R. Repression of primordial germ cell differentiation parallels germ line stem cell maintenance. Curr. Biol. 14, 981–986 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. Rodrigues, A. B., Werner, E. & Moses, K. Genetic and biochemical analysis of the role of Egfr in the morphogenetic furrow of the developing Drosophila eye. Development 132, 4697–4707 (2005)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank J. Treisman for her support with both materials and ideas; G. Dietzl and B. Dickson for sharing UAS-SpiRNAi before publication; B. Edgar and L. Johnston for materials; J. Lafaille for discussions; S. Burden and J. Morris for critical reading of the manuscript; and C. Navarro, D. Siekhaus and all members of the Lehmann laboratory for comments on the manuscript. The Bloomington Stock Center provided reagents. L.G. is supported by a fellowship from the Helen and Martin Kimmel Center for Stem Cell Biology. R.L. is a Howard Hughes Medical Institute investigator.

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Correspondence to Ruth Lehmann.

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Supplementary information

Supplementary Figure 1

This Supplementary Figure shows the gonadal expression pattern of the protein Traffic Jam during larval development in wild type and in EgfrCA gonads. (PDF 96 kb)

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Gilboa, L., Lehmann, R. Soma–germline interactions coordinate homeostasis and growth in the Drosophila gonad. Nature 443, 97–100 (2006). https://doi.org/10.1038/nature05068

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