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The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through Notch activation

Nature Genetics volume 24, pages 429–433 (2000)Cite this article

Abstract

Recent studies in vertebrates and Drosophila melanogaster have revealed that Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis1,2. In these processes, a homeobox-containing transcription factor is responsible for spatially regulating fringe (fng) expression and thus directing activation of the Notch pathway along the fng expression border. Here we show that this may be a general mechanism for patterning epithelial cell layers. At three stages in Drosophila oogenesis, mirror (mirr) and fng have complementary expression patterns in the follicle-cell epithelial layer, and at all three stages loss of mirr enlarges, and ectopic expression of mirr restricts, fng expression, with consequences for follicle-cell patterning. These morphological changes are similar to those caused by Notch mutations. Ectopic expression of mirr in the posterior follicle cells induces a stripe of rhomboid (rho) expression and represses pipe (pip), a gene with a role in the establishment of the dorsal-ventral axis, at a distance. Ectopic Notch activation has a similar long-range effect on pip. Our results suggest that Mirror and Notch induce secretion of diffusible morphogens and we have identified TGF-β (encoded by dpp) as such a molecule in germarium. We also found that mirr expression in dorsal follicle cells is induced by the EGF-receptor (EGFR) pathway and that mirr then represses pip expression in all but the ventral follicle cells, connecting EGFR activation in the dorsal follicle cells to repression of pip in the dorsal and lateral follicle cells. Our results suggest that the differentiation of ventral follicle cells is not a direct consequence of germline signalling, but depends on long-range signals from dorsal follicle cells, and provide a link between early and late events in Drosophila embryonic dorsal-ventral axis formation.

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Figure 1: The expression patterns of mirr and fng are complementary during Drosophila oogenesis.
Figure 2: mirr function is required for encapsulation in the germarium, differentiation of terminal follicle cells at stage 6 and establishment of dorsal-ventral polarity at stages 8–10.
Figure 3: MIRR and constitutively active Notch affect pip expression at a distance.
Figure 4: dpp is expressed in the germarium near a region of Notch activity in a Notch-dependent manner.
Figure 5: Model for MIRR function at stage 9 in oogenesis.

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Acknowledgements

We thank S. Parkhurst, C. Berg and D. Baker for helpful comments on the manuscript; K. Irvine, G. Struhl and A. Spradling for reagents; and K. Fischer for technical help. This work was supported by grants from the Established Investigatorship Award from the American Heart Association, March of Dimes Birth Defect Foundation, Basil O'Conner Starter Research Grant, National Institutes of Health, and Pew Memorial Trust, Pew Scholarship in the Biomedical Sciences to H.R.-B. K.C.J. was supported by grants from NIH, Cell Cytotherapeutics and the Benjamin Schultz Fellowship.

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Authors and Affiliations

  1. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA

    Katherine C. Jordan & Hannele Ruohola-Baker

  2. Department of Biochemistry and Center for Developmental Biology, University of Washington, Seattle, Washington, USA

    Katherine C. Jordan, Nigel J. Clegg, Jennifer A. Blasi, Alyssa M. Morimoto, Wu-Min Deng, Michael Tworoger & Hannele Ruohola-Baker

  3. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA

    Jonaki Sen & David Stein

  4. Developmental Patterning Laboratory, ICRF, London, UK

    Helen McNeill

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Correspondence to Hannele Ruohola-Baker.

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Jordan, K., Clegg, N., Blasi, J. et al. The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through Notch activation. Nat Genet 24, 429–433 (2000). https://doi.org/10.1038/74294

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