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.

  • Letter
  • Published:

Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila

Abstract

During metazoan development, cell-fate diversity is brought about, in part, by asymmetric cell divisions1. In Drosophila, bristle mechanosensory organs are composed of four different cells that originate from a single precursor cell, pI, after two rounds of asymmetric division2. At each division, distinct fates are conferred on sister cells by the asymmetric segregation of Numb, a negative regulator of Notch signalling3,4,5,6. Here we show that the orientation of the mitotic spindles and the localization of the Numb crescent follow a stereotyped pattern. Mitosis of pI is orientated parallel to the anteroposterior axis of the fly. We show that signalling mediated by the Frizzled receptor polarizes pI along this axis, thereby specifying the orientation of the mitotic spindle and positioning the Numb crescent. The mitoses of the two cells produced by mitosis of pI are orientated parallel and orthogonal, respectively, to the division axis of pI. This difference in cell-division orientation is largely independent of the identity of the secondary precursor cells, and is regulated by Frizzled-independent mechanisms.

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

Access options

Buy this article

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

Figure 1: Orientation of cell divisions in the bristle lineage.
Figure 2: The orientation of the pIIb division is largely independent of its cell identity.
Figure 3: Orientation of cell divisions in fz and dsh mutant pupae.

Similar content being viewed by others

References

  1. Horvitz, H. & Herskowitz, I. Mechanisms of asymmetric cell division: two Bs or not two Bs, that is the question. Cell 68, 237–255 (1992).

    Article  CAS  Google Scholar 

  2. Hartenstein, V. & Posakony, J. W. Development of adult sensilla on the wing and notum of Drosophila melanogaster. Development 107, 398–405 (1989).

    Google Scholar 

  3. Rhyu, M. S., Jan, L. Y. & Jan, Y. N. Asymmetric distribution of Numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells. Cell 76, 477–491 (1994).

    Article  CAS  Google Scholar 

  4. Knoblich, J. A., Jan, L. Y. & Jan, Y. N. Asymmetric segregation of Numb and Prospero during cell division. Nature 377, 624–627 (1995).

    Article  ADS  CAS  Google Scholar 

  5. Frise, E., Knoblich, J. A., Younger-Shepherd, S., Jan, L. Y. & Jan, Y. N. The Drosophila Numb protein inhibits signaling of the Notch receptor during cell-cell interaction in sensory organ lineage. Proc. Natl Acad. Sci. USA 93, 11925–11932 (1996).

    Article  ADS  CAS  Google Scholar 

  6. Guo, M., Jan, L. Y. & Jan, Y. N. Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Neuron 17, 27–41 (1996).

    Article  Google Scholar 

  7. Gho, M., Lecourtois, M., Géraud, G., Posakony, J. W. & Schweisguth, F. Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling. Development 122, 1673–1682 (1996).

    CAS  PubMed  Google Scholar 

  8. Wang, S., Younger-Shepherd, S., Jan, L. Y. & Jan, Y. N. Only a subset of binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless. Development 124, 4435–4446 (1997).

    CAS  PubMed  Google Scholar 

  9. Lawrence, P. A. Gradients in the insect segment: the orientation of hairs in the milkweed bug Oncopeltus fasciatus. J. Exp. Biol. 44, 607–620 (1996).

    Google Scholar 

  10. Bate, C. M. in Handbook of Sensory Physiology (ed. Jakobson, M.) 1–52 (Springer, Berlin, 1978).

    Google Scholar 

  11. Lieber, T., Kidd, S., Alcano, E., Corbin, V. & Young, M. W. Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. Genes Dev. 7, 1949–1965 (1993).

    Article  CAS  Google Scholar 

  12. Adler, P. N. The genetic control of tissue polarity in Drosophila. Bioessays 14, 735–741 (1992).

    Article  CAS  Google Scholar 

  13. Park, W.-J., Lin, J. & Adler, P. N. The frizzled gene of Drosophila encodes a membrane protein with an odd number of transmembrane domains. Mech. Dev. 45, 127–137 (1994).

    Article  CAS  Google Scholar 

  14. Krasnow, R. E., Wong, L. L. & Adler, P. N. dishevelled is a component of the frizzled signaling pathway in Drosophila. Development 121, 4095–4102 (1996).

    Google Scholar 

  15. Jones, K. H., Lin, J. & Adler, P. N. Molecular analysis of EMS-induced frizzled mutations in Drosophila melanogaster. Genetics 142, 205–215 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Gonczy, P. & Hyman, A. Cortical domains and the mechanisms of asymmetric cell division. Trends Cell Biol. 6, 382–387 (1996).

    Article  CAS  Google Scholar 

  17. Kraut, R., Chia, W., Jan, L. Y., Jan, Y. N. & Knoblich, J. A. Role of inscuteable in orientating asymmetric cell divisions in Drosophila. Nature 383, 50–55 (1996).

    Article  ADS  CAS  Google Scholar 

  18. Thorpe, C. J., Schlesinger, A., Clayton Carter, J. & Bowerman, B. Wnt signaling polarizes an early C.elegans blastomere to distinguish endoderm from mesoderm. Cell 90, 695–705 (1997).

    Article  CAS  Google Scholar 

  19. Rocheleau, C.et al. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90, 707–716 (1997).

    Article  CAS  Google Scholar 

  20. Sawa, H., Lobel, L. & Horvitz, H. R. The Caenorhabditis elegans lin-17, which is required for certain asymmetric cell division, encodes a putative seven-transmembrane protein similar to the Drosophila Frizzled protein. Genes Dev. 10, 2189–2197 (1996).

    Article  CAS  Google Scholar 

  21. Usui, K. & Kimura, K. Sequential emergence of the evenly spaced microchaetes on the notum of Drosophila. Arch. Dev. Biol. 203, 151–158 (1993).

    Article  Google Scholar 

  22. Emery, J. F. & Bier, E. Specificity of CNS and PNS regulatory subelements comprising pan-neural enhancers of the deadpan and scratch genes is achieved by repression. Development 121, 3549–3560 (1995).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank P. Adler, E. Bier, D.Coen, F. Chanut, C. Doe, Y.-N. Jan, T. Lieber and the Developmental Studies Hybridoma Bank for flies and antibodies; F. Rosa and M. Wassef for critical reading of the manuscript; and the Imaging facility of the Institut Jacques Monod for use of confocal microscopes. This work was supported by grants from the CNRS, the MENESR, the Fondation pour la Recherche Medicale, the Association pour la Recherche contre le Cancer and the Ligue Nationale contre le Cancer — Comité de Paris.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michel Gho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gho, M., Schweisguth, F. Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature 393, 178–181 (1998). https://doi.org/10.1038/30265

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/30265

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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