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Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila

Nature volume 426, pages 555–559 (2003)Cite this article

A Corrigendum to this article was published on 25 March 2004

Abstract

Drosophila thoracic mechanosensory bristles originate from cells that are singled out from ‘proneural’ groups of competent epithelial cells. Neural competence is restricted to individual sensory organ precursors (SOPs) by Delta/Notch-mediated ‘lateral inhibition’, whereas other cells in the proneural field adopt an epidermal fate. The precursors of the large macrochaetes differentiate separately from individual proneural clusters that comprise about 20–30 cells or as heterochronic pairs from groups of more than 100 cells1, whereas the precursors of the small regularly spaced microchaetes emerge from even larger proneural fields2. This indicates that lateral inhibition might act over several cell diameters; it was difficult to reconcile with the fact that the inhibitory ligand Delta is membrane-bound until the observation that SOPs frequently extend thin processes3,4 offered an attractive hypothesis. Here we show that the extension of these planar filopodia—a common attribute of wing imaginal disc cells—is promoted by Delta and that their experimental suppression reduces Notch signalling in distant cells and increases bristle density in large proneural groups, showing that these membrane specializations mediate long-range lateral inhibition.

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Figure 1: Confocal imaging of anti-GFP immunofluorescent labelling of wing disc cells expressing CD8–GFP (a–c, e–i) or Delta–GFP (d) at the puparium formation stage unless otherwise stated.
Figure 2: Effect of ezrin-DN and Delta on the extent of SOP filopodia web.
Figure 3: Effect of ezrin-DN and Delta expression in SOPs on the range of lateral inhibition.

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Acknowledgements

This work was initiated in the unité INSERM 432, Université Montpellier II. We thank S. Baghdiguian, C. Dambly-Chaudière, A. Ghysen, S. Layalle, P.-H. Mangeat and A.-M. Martinez for discussions; C. Dambly-Chaudière, M. Haenlin, F. Schweisguth, J.-P. Vincent, the Bloomington Stock Center and the Developmental Studies Hybridoma Bank for fly stocks and reagents; N. Lautrédou-Audouy for help with confocal microscopy; F. Mérezègue for help with electron microscopy; E. Gazave and A. Sahuquet for help with morphometry and statistics; and C. Roy for critically reading the manuscript. C.d.J. and D.A. thank the researchers into Drosophila at the Institut de Génétique Humaine (Montpellier) for hospitality. This work was supported by grants to D.A. from the Association pour la Recherche contre le Cancer and the Université Montpellier II. C.d.J. was supported by the Fondation pour la Recherche Médicale.

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  1. Jonathan Soulé and Marianne Martin: These authors contributed equally to this work

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  1. Laboratoire Dynamique Moléculaire des Interactions Membranaires, UMR 5539, Université Montpellier II C.C. 107, Place Eugène Bataillon, 34095 5, Montpellier cedex, France

    Cyrille de Joussineau, Jonathan Soulé, Marianne Martin, Christelle Anguille, Philippe Montcourrier & Daniel Alexandre

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  1. Cyrille de Joussineau
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Correspondence to Daniel Alexandre.

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de Joussineau, C., Soulé, J., Martin, M. et al. Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila. Nature 426, 555–559 (2003). https://doi.org/10.1038/nature02157

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