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Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye

Nature volume 397, pages 523–526 (1999)Cite this article

Abstract

Planar polarity is seen in epidermally derived structures throughout the animal kingdom1,2. In the Drosophila eye, planar polarity is reflected in the mirror-symmetric arrangement of ommatidia (eye units) across the dorsoventral midline or equator; ommatidia on the dorsal and ventral sides of the equator exhibit opposite chirality3,4,5. Photoreceptors R3 and R4 are essential in the establishment of the polarity of ommatidia6,7,8,9,10,11. The R3 cell is thought to receive the polarizing signal, through the receptor Frizzled (Fz), before or at higher levels then the R4 cell, generating a difference between neighbouring R3 and R4 cells6,7,9,10. Both loss-of-function and overexpression of Fz in the R3/R4 pair result in polarity defects and loss of mirror-image symmetry6,7,9,10,12. Here we identify Notch and Delta (Dl) as dominant enhancers of the phenotypes produced by overexpression of fz and dishevelled (dsh), which encodes a signalling component downstream of Fz, and we show that Dl-mediated activation of Notch is required for establishment of ommatidial polarity. Whereas fz signalling is required to specify R3, Notch signalling induces the R4 fate. Our data indicate that Dl is a transcriptional target of Fz/Dsh signalling in R3, and activates Notch in the neighbouring R4 precursor. This two-tiered mechanism explains how small differences in the level and/or timing of Fz activation reliably generate a binary cell-fate decision, leading to specification of R3 and R4 and ommatidial chirality.

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Figure 1: Dl and Notch dominantly enhance an eye-polarity-specific fz gain-of-function phenotype.
Figure 2: Notch signalling is required for the establishment of ommatidial chirality.
Figure 3: Fz and Notch signalling are sufficient to autonomously induce the R3 and R4 fates, respectively.
Figure 4: Dl expression in the R3/R4 pair is regulated by Fz signalling.

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References

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

    Article  CAS  Google Scholar 

  2. Eaton, S. Planar polarization in Drosophila and vertebrate epithelia. Curr. Opin. Cell Biol. 9, 860–866 (1997).

    Article  CAS  Google Scholar 

  3. Tomlinson, A. Cellular interactions in the developing Drosophila eye. Development 104, 183–193 (1988).

    CAS  PubMed  Google Scholar 

  4. Ready, D. F. Amultifaceted approach to neural development. Trends Neurosci. 12, 102–110 (1989).

    Article  CAS  Google Scholar 

  5. Wolff, T. & Ready, D. F. in The Development of Drosophila melanogaster(eds Martinez-Arias, A. & Bate, M.) 1277–1326 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, (1993)).

    Google Scholar 

  6. Zheng, L., Zhang, J. & Carthew, R. W. frizzled regulates mirror-symmetric pattern formation in the Drosophila eye. Development 121, 3045–3055 (1995).

    CAS  PubMed  Google Scholar 

  7. Boutros, M., Paricio, N., Strutt, D. I. & Mlodzik, M. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell 94, 109–118 (1998).

    Article  CAS  Google Scholar 

  8. Fanto, M., Mayes, C. A. & Mlodzik, M. Linking cell-fate specification to planar polarity: determination of the R3/R4 photoreceptors is a prerequisite for the interpretation of the Frizzled mediated polarity signal. Mech. Dev. 74, 51–58 (1998).

    Article  CAS  Google Scholar 

  9. Strutt, D. I., Weber, U. & Mlodzik, M. The role of RhoA in tissue polarity and Frizzled signalling. Nature 387, 292–295 (1997).

    Article  ADS  CAS  Google Scholar 

  10. Tomlinson, A., Strapps, W. R. & Heemskerk, J. Linking Frizzled and Wnt signaling in Drosophila development. Development 124, 4515–4521 (1997).

    CAS  PubMed  Google Scholar 

  11. Wolff, T. & Rubin, G. M. strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila. Development 125, 1149–1159 (1998).

    CAS  PubMed  Google Scholar 

  12. Gubb, D. Genes controlling cellular polarity in Drosophila. Development Suppl., 269–277 (1993).

    Google Scholar 

  13. Theisen, H. et al. dishevelled is required during wingless signalling to establish both cell polarity and cell identity. Development 120, 347–360 (1994).

    CAS  PubMed  Google Scholar 

  14. Bhanot, P. et al. Anew member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382, 225–230 (1996).

    Article  ADS  CAS  Google Scholar 

  15. Krasnow, R. E., Wong, L. L. & Adler, P. N. dishevelled is a component of the frizzled signaling pathway in Drosophila. Development 121, 4095–4102 (1995).

    CAS  PubMed  Google Scholar 

  16. Axelrod, J. D., Miller, J. R., Shulman, J. M., Moon, R. T. & Perrimon, N. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 12, 2610–2622 (1998).

    Article  CAS  Google Scholar 

  17. Artavanis-Tsakonas, S., Matsuno, K. & Fortini, M. Notch signaling. Science 268, 225–232 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Cagan, R. L. & Ready, D. F. Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev. 3, 1099–1112 (1989).

    Article  CAS  Google Scholar 

  19. Fortini, M. E., Simon, M. A. & Rubin, G. M. Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation. Nature 355, 559–561 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Baker, N. E. & Zitron, A. E. Drosophila eye development: Notch and Delta amplify a neurogenic pattern conferred on the morphogenetic furrow by scabrous. Mech. Dev. 49, 173–189 (1995).

    Article  CAS  Google Scholar 

  21. Baker, N. E., Sung, Y. & Han, D. Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye. Curr. Biol. 6, 1290–1301 (1996).

    Article  CAS  Google Scholar 

  22. Papayannopoulos, V., Tomlinson, A., Panin, V. M., Rauskolb, C. & Irvine, K. D. Dorsal-ventral signaling in the Drosophila eye. Science 281, 2031–2034 (1998).

    Article  ADS  CAS  Google Scholar 

  23. Cho, K. -O. K. & Choi, K. W. Fringe is essential for mirror symmetry and morphogenesis in the Drosophila eye. Nature 396, 272–276 (1998).

    Article  ADS  CAS  Google Scholar 

  24. Dominguez, M. & de Celis, J. F. Adorsal/ventral boundary established by Notch controls growth and polarity in the Drosophila eye. Nature 396, 276–278 (1998).

    Article  ADS  CAS  Google Scholar 

  25. Parks, A. L., Turner, F. R. & Muskavitch, M. A. T. Relationships between complex Delta expression and the specificaiton of retinal cell fates during Drosophila eye development. Mech. Dev. 50, 201–216 (1995).

    Article  CAS  Google Scholar 

  26. Mlodzik, M., Hiromi, Y., Weber, U., Goodman, C. S. & Rubin, G. M. The Drosophila seven-up gene, a member of the steroid receptor gene superfamily, controls photoreceptor cell fates. Cell 60, 211–224 (1990).

    Article  CAS  Google Scholar 

  27. Campuzano, S. & Modolell, J. Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet. 8, 202–208 (1992).

    Article  CAS  Google Scholar 

  28. Chen, C. W. J., Jung, H. S., Jiang, T. X. & Chuong, C. M. Asymmetric expression of Notch/Delta/Serrate is associated with the anterior-posterior axis of feather buds. Dev. Biol. 188, 181–188 (1997).

    Article  CAS  Google Scholar 

  29. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  Google Scholar 

  30. Tomlinson, A. & Ready, D. F. Neuronal differentiation in the Drosophila ommatidium. Dev. Biol. 120, 366–376 (1987).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R. Bario, M. Fortini, M. Haenlin, J. Royet, M. Milan, M. Muskavitch, A.Parks, G. M. Rubin and the Bloomington stock center for fly strains and antibodies; M. Fortini and S.Bray for sharing unpublished results and discussion; A. Cyrklaff for chromosome in situ mapping; C.Blaumueller and J. Curtiss for comments on the manuscript; and members of the Mlodzik laboratory for stimulating discussions.

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  1. Marek Mlodzik: Correspondence and requests for materials should be addressed to M.M.

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  1. Developmental Biology Programme, EMBL, Meyerhofstrasse 1, 69117, Heidelberg, Germany

    Manolis Fanto & Marek Mlodzik

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  1. Manolis Fanto
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Fanto, M., Mlodzik, M. Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye. Nature 397, 523–526 (1999). https://doi.org/10.1038/17389

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