Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

ftz-f1 and Hr39 opposing roles on EcR expression during Drosophila mushroom body neuron remodeling

Nature Neuroscience volume 14, pages 37–44 (2011)Cite this article

Subjects

Abstract

Developmental axon pruning is a general mechanism that is required for maturation of neural circuits. During Drosophila metamorphosis, the larval-specific dendrites and axons of early γ neurons of the mushroom bodies are pruned and replaced by adult-specific processes. We found that the nuclear receptor ftz-f1 is required for this pruning, activates expression of the steroid hormone receptor EcR-B1, whose activity is essential for γ remodeling, and represses expression of Hr39, an ftz-f1 homologous gene. If inappropriately expressed in the γ neurons, HR39 inhibits normal pruning, probably by competing with endogenous FTZ-F1, which results in decreased EcR-B1 expression. EcR-B1 was previously identified as a target of the TGFβ signaling pathway. We found that the ftz-f1 and Hr39 pathway apparently acts independently of TGFβ signaling, suggesting that EcR-B1 is the target of two parallel molecular pathways that act during γ neuron remodeling.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: βFTZ-F1 is required for γ neuron pruning.
Figure 2: HR39 ectopic expression blocks γ neuron remodeling.
Figure 3: Forced expression of ECR-B1 rescues ftz-f1−/− and HR39 overexpression γ neuronal remodeling defects.
Figure 4: Expression of ECR-B1 depends on normal FTZ-F1 and lack of HR39 activity in γ neurons.
Figure 5: FTZ-F1 represses Hr39 expression to prevent competition.
Figure 6: Hr39 is required for normal αβ neuron development, but not for γ pruning.
Figure 7: In vivo binding of FTZ-F1 upstream of the EcR-B1 transcription start site.

Similar content being viewed by others

References

  1. Williams, D.W. & Truman, J.W. Remodeling dendrites during insect metamorphosis. J. Neurobiol. 64, 24–33 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Luo, L. & O'Leary, D.D. Axon retraction and degeneration in development and disease. Annu. Rev. Neurosci. 28, 127–156 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Lee, T., Marticke, S., Sung, C., Robinow, S. & Luo, L. Cell-autonomous requirement of the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling in Drosophila. Neuron 28, 807–818 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Zheng, X. et al. TGF-beta signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain. Cell 112, 303–315 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Watts, R.J., Hoopfer, E.D. & Luo, L. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron 38, 871–885 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Awasaki, T. et al. The Drosophila trio plays an essential role in patterning of axons by regulating their directional extension. Neuron 26, 119–131 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Watts, R.J., Schuldiner, O., Perrino, J., Larsen, C. & Luo, L. Glia engulf degenerating axons during developmental axon pruning. Curr. Biol. 14, 678–684 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Awasaki, T. et al. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis. Neuron 50, 855–867 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Schuldiner, O. et al. piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning. Dev. Cell 14, 227–238 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hoopfer, E.D., Penton, A., Watts, R.J. & Luo, L. Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein Boule as a negative regulator of axon pruning. J. Neurosci. 28, 6092–6103 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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. Development 124, 761–771 (1997).

    CAS  PubMed  Google Scholar 

  12. Lee, T., Lee, A. & Luo, L. Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast. Development 126, 4065–4076 (1999).

    CAS  PubMed  Google Scholar 

  13. Williams, D.W. & Truman, J.W. Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons. Development 132, 3631–3642 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Brown, H.L., Cherbas, L., Cherbas, P. & Truman, J.W. Use of time-lapse imaging and dominant negative receptors to dissect the steroid receptor control of neuronal remodeling in Drosophila. Development 133, 275–285 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. King-Jones, K. & Thummel, C.S. Nuclear receptors—a perspective from Drosophila. Nat. Rev. Genet. 6, 311–323 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Horner, M.A., Chen, T. & Thummel, C.S. Ecdysteroid regulation and DNA binding properties of Drosophila nuclear hormone receptor superfamily members. Dev. Biol. 168, 490–502 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Yamada, M. et al. Temporally restricted expression of transcription factor betaFTZ-F1: significance for embryogenesis, molting and metamorphosis in Drosophila melanogaster. Development 127, 5083–5092 (2000).

    CAS  PubMed  Google Scholar 

  18. Sullivan, A.A. & Thummel, C.S. Temporal profiles of nuclear receptor gene expression reveal coordinate transcriptional responses during Drosophila development. Mol. Endocrinol. 17, 2125–2137 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Ayer, S. et al. Activation and repression of Drosophila alcohol dehydrogenase distal transcription by two steroid hormone receptor superfamily members binding to a common response element. Nucleic Acids Res. 21, 1619–1627 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ohno, C.K., Ueda, H. & Petkovich, M. The Drosophila nuclear receptors FTZ-F1 alpha and FTZ-F1 beta compete as monomers for binding to a site in the fushi tarazu gene. Mol. Cell. Biol. 14, 3166–3175 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Crispi, S., Giordano, E., D'Avino, P.P. & Furia, M. Cross-talking among Drosophila nuclear receptors at the promiscuous response element of the ng-1 and ng-2 intermolt genes. J. Mol. Biol. 275, 561–574 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Guichet, A. et al. The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Nature 385, 548–552 (1997).

    Article  CAS  PubMed  Google Scholar 

  23. Yang, M.Y., Armstrong, J.D., Vilinsky, I., Strausfeld, N.J. & Kaiser, K. Subdivision of the Drosophila mushroom bodies by enhancer-trap expression patterns. Neuron 15, 45–54 (1995).

    Article  PubMed  Google Scholar 

  24. Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451–461 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. Wang, J., Zugates, C.T., Liang, I.H., Lee, C.H. & Lee, T. Drosophila Dscam is required for divergent segregation of sister branches and suppresses ectopic bifurcation of axons. Neuron 33, 559–571 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Murata, T., Kageyama, Y., Hirose, S. & Ueda, H. Regulation of the EDG84A gene by FTZ-F1 during metamorphosis in Drosophila melanogaster. Mol. Cell. Biol. 16, 6509–6515 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bellen, H.J. et al. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167, 761–781 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Horner, M. & Thummel, C.S. Mutations in the DHR39 orphan receptor gene have no effect on viability. Drosoph. Inf. Serv. 80, 35–37 (1997).

    Google Scholar 

  29. Allen, A.K. & Spradling, A.C. The Sf1-related nuclear hormone receptor Hr39 regulates Drosophila female reproductive tract development and function. Development 135, 311–321 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Lavorgna, G., Karim, F.D., Thummel, C.S. & Wu, C. Potential role for a FTZ-F1 steroid receptor superfamily member in the control of Drosophila metamorphosis. Proc. Natl. Acad. Sci. USA 90, 3004–3008 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lam, G. & Thummel, C.S. Inducible expression of double-stranded RNA directs specific genetic interference in Drosophila. Curr. Biol. 10, 957–963 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Ueda, H., Sonoda, S., Brown, J.L., Scott, M.P. & Wu, C. A sequence-specific DNA-binding protein that activates fushi tarazu segmentation gene expression. Genes Dev. 4, 624–635 (1990).

    Article  CAS  PubMed  Google Scholar 

  33. Ueda, H. & Hirose, S. Defining the sequence recognized with BmFTZ-F1, a sequence specific DNA binding factor in the silkworm, Bombyx mori, as revealed by direct sequencing of bound oligonucleotides and gel mobility shift competition analysis. Nucleic Acids Res. 19, 3689–3693 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Thummel, C.S. Molecular mechanisms of developmental timing in C. elegans and Drosophila. Dev. Cell 1, 453–465 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Mehren, J.E., Ejima, A. & Griffith, L.C. Unconventional sex: fresh approaches to courtship learning. Curr. Opin. Neurobiol. 14, 745–750 (2004).

    Article  CAS  PubMed  Google Scholar 

  36. Davis, R.L. Olfactory memory formation in Drosophila: from molecular to systems neuroscience. Annu. Rev. Neurosci. 28, 275–302 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Gonzy-Tréboul, G., Lepesant, J.A. & Deutsch, J. Enhancer-trap targeting at the Broad Complex locus of Drosophila melanogaster. Genes Dev. 9, 1137–1148 (1995).

    Article  PubMed  Google Scholar 

  38. Nicolaï, M., Lasbleiz, C. & Dura, J.M. Gain-of-function screen identifies a role of the Src64 oncogene in Drosophila mushroom body development. J. Neurobiol. 57, 291–302 (2003).

    Article  PubMed  Google Scholar 

  39. Robertson, H.M. et al. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics 118, 461–470 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Engels, W.R., Johnson-Schlitz, D.M., Eggleston, W.B. & Sved, J. High-frequency P element loss in Drosophila is homolog dependent. Cell 62, 515–525 (1990).

    Article  CAS  PubMed  Google Scholar 

  41. Talbot, W.S., Swyryd, E.A. & Hogness, D.S. Drosophila tissues with different metamorphic responses to ecdysone express different ecdysone receptor isoforms. Cell 73, 1323–1337 (1993).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are particularly grateful to L. Fradkin for helpful discussions and comments on the manuscript. We thank L. Luo and T. Lee for babo, usp and several MARCM stocks; H. Ueda for the ftz-f1ex7FRT2A stock, the pUAST–βftz-f1 vector and the antibody to FTZ-F1; C. Woodard for the ftz-f119 stock; L. Pick for the UAS–αftz-f1 stock and the GST–FTZ-F1 expression vector; C. Thummel for the antibody to ECR-B1 (ascite fluid); B. Dickson for the antibody to TRIO; M. O'Connor for the UAS-babo-act (1B3 strong) and the UAS-baboΔI (2 transgenes 5A2–8A2) stocks and unpublished data pertaining to antibody to BABO and to babo transcripts and K. Matthews and K. Cook at the Bloomington Drosophila Stock Center. We also thank N. Lautredou at the Centre Régional d'Imagerie Cellulaire and J. Cau at the “Plateau d'Imagerie Cellulaire” for help with confocal imaging and P. Atger and C. Sarrauste de Menthière at the “service iconographie IGH”. Transgenic lines were generated by BestGene. This work was supported by the CNRS, grants from the Fondation pour la Recherche Médicale, the EEC Marie Curie 5th framework, the Association pour la Recherche sur le Cancer (n° 3744), the Association Française contre les Myopathies (MNM1 2007) and the Agence Nationale de la Recherche (ANR-07-NEURO-034-01). A.B. was supported by a postdoctoral fellowship from Fondation pour la Recherche Médicale, EEC Marie Curie 5th framework, from Association Française contre les Myopathies Agence Nationale de la Recherche. C.C.-R. was supported by a joint Ph.D. grant from the CNRS and Région Languedoc-Roussillon and then by a predoctoral Association pour la Recherche sur le Cancer fellowship.

Author information

Author notes

  1. Ana Boulanger and Christelle Clouet-Redt: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Human Genetics, CNRS UPR1142, Montpellier, France

    Ana Boulanger, Christelle Clouet-Redt, Morgane Farge, Adrien Flandre, Thomas Guignard & Jean-Maurice Dura

  2. Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Montpellier, France

    Céline Fernando & François Juge

  3. Université Montpellier 2, Montpellier, France

    Céline Fernando & François Juge

  4. Université Montpellier 1, Montpellier, France

    Céline Fernando & François Juge

Authors
  1. Ana Boulanger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christelle Clouet-Redt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Morgane Farge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adrien Flandre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Guignard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Céline Fernando
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. François Juge
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jean-Maurice Dura
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.B., C.C.-R. and J.-M.D. designed the experiments and analyzed the data. C.F. and F.J. performed the chromatin immunoprecipitation experiments. J.-M.D. carried out the elaboration of the genetic stocks. A.B., C.C.-R., M.F., A.F. and T.G. performed all of the other experiments. The manuscript was written by J.-M.D. and commented on by A.B., C.C.-R. and A.F.

Corresponding author

Correspondence to Jean-Maurice Dura.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–16 and List of Fly Strains (PDF 1302 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boulanger, A., Clouet-Redt, C., Farge, M. et al. ftz-f1 and Hr39 opposing roles on EcR expression during Drosophila mushroom body neuron remodeling. Nat Neurosci 14, 37–44 (2011). https://doi.org/10.1038/nn.2700

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.2700

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing