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:

Antagonistic roles of Wnt5 and the Drl receptor in patterning the Drosophila antennal lobe

Nature Neuroscience volume 10, pages 1423–1432 (2007)Cite this article

Abstract

Numerous studies have shown that ingrowing olfactory axons exert powerful inductive influences on olfactory map development. From an overexpression screen, we have identified wnt5 as a potent organizer of the olfactory map in Drosophila melanogaster. Loss of wnt5 resulted in severe derangement of the glomerular pattern, whereas overexpression of wnt5 resulted in the formation of ectopic midline glomeruli. Cell type–specific cDNA rescue and mosaic experiments showed that wnt5 functions in olfactory neurons. Mutation of the derailed (drl) gene, encoding a receptor for Wnt5, resulted in derangement of the glomerular map, ectopic midline glomeruli and the accumulation of Wnt5 at the midline. We show here that drl functions in glial cells, where it acts upstream of wnt5 to modulate its function in glomerular patterning. Our findings establish wnt5 as an anterograde signal that is expressed by olfactory axons and demonstrate a previously unappreciated, yet powerful, role for glia in patterning the Drosophila olfactory map.

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: The olfactory map is disrupted in the wnt5 mutant.
Figure 2: Wnt5 functions during antennal lobe development and localizes to projection neuron dendrites.
Figure 3: wnt5 functions in the ORNs.
Figure 4: The olfactory map is disrupted in the drl mutant.
Figure 5: Drl functions during antennal lobe development and localizes to TIFR glia.
Figure 6: Drl functions in glial cells and its WIF domain is essential.
Figure 7: drl functions upstream of wnt5 to inhibit wnt5 function.
Figure 8: Wnt5 is localized in the antennal lobe neuropil and midline commissure in the drl mutant animals.

Similar content being viewed by others

References

  1. Mombaerts, P. Axonal wiring in the mouse olfactory system. Annu. Rev. Cell Dev. Biol. 22, 713–737 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Dynes, J.L. & Ngai, J. Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed by dynamic imaging in living zebrafish embryos. Neuron 20, 1081–1091 (1998).

    Article  CAS  PubMed  Google Scholar 

  3. Potter, S.M. et al. Structure and emergence of specific olfactory glomeruli in the mouse. J. Neurosci. 21, 9713–9723 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Miyasaka, N. et al. Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system. Development 132, 1283–1293 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Lin, D.M. & Ngai, J. Development of the vertebrate main olfactory system. Curr. Opin. Neurobiol. 9, 74–78 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Hummel, T. et al. Axonal targeting of olfactory receptor neurons in Drosophila is controlled by Dscam. Neuron 37, 221–231 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Hummel, T. & Zipursky, S.L. Afferent induction of olfactory glomeruli requires N-cadherin. Neuron 42, 77–88 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Key, B. & St John, J. Axon navigation in the mammalian primary olfactory pathway: where to next? Chem. Senses 27, 245–260 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Ang, L.H., Kim, J., Stepensky, V. & Hing, H. Dock and Pak regulate olfactory axon pathfinding in Drosophila. Development 130, 1307–1316 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Lattemann, M. et al. Semaphorin-1a controls receptor neuron-specific axonal convergence in the primary olfactory center of Drosophila. Neuron. 53, 169–184 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Sweeney, L.B. et al. Temporal target restriction of olfactory receptor neurons by Semaphorin-1a/PlexinA-mediated axon-axon interactions. Neuron. 53, 185–200 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Oland, L.A., Orr, G. & Tolbert, L.P. Construction of a protoglomerular template by olfactory axons initiates the formation of olfactory glomeruli in the insect brain. J. Neurosci. 10, 2096–2112 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Stout, R.P. & Graziadei, P.P. Influence of the olfactory placode on the development of the brain in Xenopus laevis (Daudin). I. Axonal growth and connections of the transplanted olfactory placode. Neuroscience 5, 2175–2186 (1980).

    Article  CAS  PubMed  Google Scholar 

  14. Ang, L.H. et al. Lim kinase regulates the development of olfactory and neuromuscular synapses. Dev. Biol. 293, 178–190 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Graziadei, P.P. & Kaplan, M.S. Regrowth of olfactory sensory axons into transplanted neural tissue. 1. Development of connections with the occipital cortex. Brain Res. 201, 39–44 (1980).

    Article  CAS  PubMed  Google Scholar 

  16. Schneiderman, A.M., Matsumoto, S.G. & Hildebrand, J.G. Trans-sexually grafted antennae influence development of sexually dimorphic neurones in moth brain. Nature 298, 844–846 (1982).

    Article  Google Scholar 

  17. Oland, L.A. & Tolbert, L.P. Multiple factors shape development of olfactory glomeruli: insights from an insect model system. J. Neurobiol. 30, 92–109 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Moon, R.T., Bowerman, B., Boutros, M. & Perrimon, N. The promise and perils of Wnt signaling through beta-catenin. Science 296, 1644–1646 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Cadigan, K.M. & Nusse, R. Wnt signaling: a common theme in animal development. Genes Dev. 11, 3286–3305 (1997).

    Article  CAS  PubMed  Google Scholar 

  20. Yoshikawa, S., McKinnon, R.D., Kokel, M. & Thomas, J.B. Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature 422, 583–588 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Fradkin, L.G. et al. The Drosophila Wnt5 protein mediates selective axon fasciculation in the embryonic central nervous system. Dev. Biol. 272, 362–375 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Srahna, M. et al. A signaling network for patterning of neuronal connectivity in the Drosophila brain. PLoS Biol. 4, e438 (2006).

    Article  Google Scholar 

  23. Zhang, D. et al. Misexpression screen for genes altering the olfactory map in Drosophila. Genesis 44, 189–201 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Jhaveri, D., Sen, A. & Rodrigues, V. Mechanisms underlying olfactory neuronal connectivity in Drosophila-the atonal lineage organizes the periphery while sensory neurons and glia pattern the olfactory lobe. Dev. Biol. 226, 73–87 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Fishilevich, E. & Vosshall, L.B. Genetic and functional subdivision of the Drosophila antennal lobe. Curr. Biol. 15, 1548–1553 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Couto, A., Alenius, M. & Dickson, B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system. Curr. Biol. 15, 1535–1547 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. Dura, J.M., Taillebourg, E. & Preat, T. The Drosophila learning and memory gene linotte encodes a putative receptor tyrosine kinase homologous to the human RYK gene product. FEBS Lett. 370, 250–254 (1995).

    Article  CAS  PubMed  Google Scholar 

  29. Simon, A.F., Boquet, I., Synguelakis, M. & Preat, T. The Drosophila putative kinase linotte (derailed) prevents central brain axons from converging on a newly described interhemispheric ring. Mech. Dev. 76, 45–55 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Jefferis, G.S., Marin, E.C., Stocker, R.F. & Luo, L. Target neuron prespecification in the olfactory map of Drosophila. Nature 414, 204–208 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Stocker, R.F., Heimbeck, G., Gendre, N. & de Belle, J.S. Neuroblast ablation in Drosophila P[Gal4] lines reveals origins of olfactory interneurons. J. Neurobiol. 32, 443–456 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Hanks, S.K., Quinn, A.M. & Hunter, T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241, 42–52 (1988).

    Article  CAS  PubMed  Google Scholar 

  33. Taillebourg, E., Moreau-Fauvarque, C., Delaval, K. & Dura, J.M. In vivo evidence for a regulatory role of the kinase activity of the linotte/derailed receptor tyrosine kinase, a Drosophila Ryk ortholog. Dev. Genes Evol. 215, 158–163 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Schlaggar, B.L. & O'Leary, D.D. Potential of visual cortex to develop an array of functional units unique to somatosensory cortex. Science 252, 1556–1560 (1991).

    Article  CAS  PubMed  Google Scholar 

  35. Lu, W., Yamamoto, V., Ortega, B. & Baltimore, D. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell 119, 97–108 (2004).

    Article  CAS  PubMed  Google Scholar 

  36. Toba, G. et al. The gene search system. A method for efficient detection and rapid molecular identification of genes in Drosophila melanogaster. Genetics 151, 725–737 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Hofbauer, A. Eine Bibliothek monoklonaler Antikorper gegen das Gehirn von Drosophila melanogaster. (University of Wurzburg, Wurzburg, 1991).

Download references

Acknowledgements

We thank the Bloomington Drosophila Stock Center for the fly lines, A. Hofbauer for the generous gift of the nc82 antibody and W. Zhou for construction of the UAS-drl transgenic fly line. This work was supported by grants from the US National Institutes of Health and the US National Institute on Deafness and other Communication Disorders (DC5408-01), the Roy J. Carver Charitable Trust (#03-27) (H.H.), ASPASIA (Netherlands Organization for Scientific Research) and Pionier grants (J.N.), and a Genomics grant (L.F. and J.N.) from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek.

Author information

Author notes

  1. Ying Yao, Yuping Wu and Chong Yin: These authors contributed equally to this work.

Authors and Affiliations

  1. Neuroscience Program, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, 61801, Illinois, USA

    Ying Yao, Rie Ozawa & Huey Hing

  2. Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, 61801, Illinois, USA

    Yuping Wu, Chong Yin & Huey Hing

  3. Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji-shi, 192-0397, Tokyo, Japan

    Toshiro Aigaki

  4. Department of Molecular Cell Biology, Laboratory of Developmental Neurobiology, Leiden University Medical Center, Einthovenweg 20, RC, 2300, Leiden, The Netherlands

    Rene R Wouda, Jasprina N Noordermeer & Lee G Fradkin

Authors
  1. Ying Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuping Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chong Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rie Ozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshiro Aigaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rene R Wouda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jasprina N Noordermeer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lee G Fradkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Huey Hing
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.Y., Y.W., C.Y. and R.O. conducted experiments in the laboratory of H.H. R.R.W. conducted experiments in the laboratory of J.N.N. L.G.F., Y.Y., Y.W. and H.H. analyzed the data. T.A. provided the P{GS} lines screened by the H.H. lab. H.H. and L.G.F. wrote the manuscript with contributions from the other authors.

Corresponding author

Correspondence to Huey Hing.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 (PDF 13688 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, Y., Wu, Y., Yin, C. et al. Antagonistic roles of Wnt5 and the Drl receptor in patterning the Drosophila antennal lobe. Nat Neurosci 10, 1423–1432 (2007). https://doi.org/10.1038/nn1993

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1993

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