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Snail is required for Delta endocytosis and Notch-dependent activation of single-minded expression

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Abstract

In the Drosophila embryo, the mesectoderm corresponds to a single row of cells abutting the mesoderm. It is specified by the expression of the single-minded (sim) gene. The information that precisely positions the sim-expressing cells along the dorso-ventral axis is incompletely understood. Previous studies have shown that Dorsal and Twist activate sim expression in a large ventral domain, while two negative regulators, Snail (Sna) and Suppressor of Hairless [Su(H)], repress sim expression in the mesoderm and neuroectoderm, respectively. Repression by Su(H) is relieved in the presumptive mesectoderm by Notch signaling. In this paper, we show that Sna also has a positive regulatory function on sim expression in the presumptive mesectoderm. This positive effect of Sna depends on the Su(H)-binding sites within the sim promoter, suggesting that Sna regulates Notch signaling. In addition, we find that Delta is endocytosed together with the extracellular domain of Notch. The endocytosis of Delta is only seen in the mesoderm and requires the activity of the sna and neuralized (neur) genes. Interestingly, the Neur-mediated endocytosis of Delta has recently been shown to be sufficient for the non-autonomous activation of Notch target genes in wing imaginal discs. We therefore propose a novel model in which Sna positions the mesectoderm via its dual regulatory activity. In this model, Sna cell-autonomously represses sim expression in the mesoderm and relieves Su(H)-dependent repression in a cell non-autonomous fashion by promoting the Neur-dependent endocytosis of Delta in the mesoderm.

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Acknowledgements

We thank H. Bellen, C. Delidakis, E. Lai, M. Leptin, M. Muskavitch, S. Roth, G. Rubin, D. St. Johnston, the Bloomington Stock Center, the Tübingen stock center and the Developmental Studies Hybridoma Bank (University of Iowa) for providing fly stocks and antibodies. We thank A. Martinez-Arias and M. Leptin for helpful discussions. We also thank Y. Bellaïche, S. Lee, V. Orgogozo and I. Stüttem for critical reading. This work was supported by specific grants from the Centre National de la Recherche Scientifique, the Ministère de la Recherche (ACI Program) and the Association pour le Recherche contre le Cancer (ARC 5575).

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  1. Véronique Morel

    Present address: Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK

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  1. Ecole Normale Supérieure, CNRS UMR 8542, 46 rue d'Ulm, 75230, Paris Cedex 05, France

    Véronique Morel, Roland Le Borgne & François Schweisguth

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  1. Véronique Morel
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  2. Roland Le Borgne
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  3. François Schweisguth
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Correspondence to François Schweisguth.

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Morel, V., Le Borgne, R. & Schweisguth, F. Snail is required for Delta endocytosis and Notch-dependent activation of single-minded expression. Dev Genes Evol 213, 65–72 (2003). https://doi.org/10.1007/s00427-003-0296-x

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