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Endocytosis by Numb breaks Notch symmetry at cytokinesis

Nature Cell Biology volume 14, pages 131–139 (2012)Cite this article

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Abstract

Cell-fate diversity can be generated by the unequal segregation of the Notch regulator Numb at mitosis in both vertebrates and invertebrates. Whereas the mechanisms underlying unequal inheritance of Numb are understood, how Numb antagonizes Notch has remained unsolved. Live imaging of Notch in sensory organ precursor cells revealed that nuclear Notch is detected at cytokinesis in the daughter cell that does not inherit Numb. Numb and Sanpodo act together to regulate Notch trafficking and establish directional Notch signalling at cytokinesis. We propose that unequal segregation of Numb results in increased endocytosis in one daughter cell, hence asymmetry of Notch at the cytokinetic furrow, directional signalling and binary fate choice.

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Figure 1: Notch localization at the pIIa/pIIb interface.
Figure 2: Live analysis of Notch signalling.
Figure 3: Regulation of Notch by Numb and Spdo at cytokinesis.
Figure 4: Notch is endocytosed from the pIIa/pIIb interface.
Figure 5: Endocytosis of Notch by Spdo.
Figure 6: Endocytosis of Spdo–Notch complexes.

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Acknowledgements

We thank O. Baudouin, K. Basler, H. Bellen, R. Bodmer, P. Bryant, S. Eaton, M. Gonzalez-Gaitan, Y. Hong, J. Knoblich, R. Le Borgne, T. Lecuit, Y. Hong, N. Perrimon, F. Roegiers, J. Skeath, R. Ueda, A. Wodarz, W. Zhong, the Bloomington Drosophila Stock Center, the Developmental Studies Hybridoma Bank, the Drosophila Genomics Resource Center and Flybase for flies, antibodies, DNA and other resources. We are very grateful to H. Rouault for the custom design of a temperature-controlled stage. We thank R. Le Borgne, A. Martinez-Arias, O. Pourquié, C. Saleh and laboratory members for discussions and critical reading. This work was funded by the Centre National de la Recherche Scientifique, Institut Pasteur, the National Agency for Research (BLAN-05-0277) and the Fondation pour la Recherche Médicale (DEQ20100318284).

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  1. Nicolas Vodovar

    Present address: Present address: Institut Pasteur, Virology Department, F-75015 Paris, France,

Authors and Affiliations

  1. Developmental Biology Department, Institut Pasteur, F-75015 Paris, France

    Lydie Couturier, Nicolas Vodovar & François Schweisguth

  2. CNRS, URA2578, F-75015 Paris, France

    Lydie Couturier, Nicolas Vodovar & François Schweisguth

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  1. Lydie Couturier
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F.S. designed the study, carried out microscopy work and wrote the manuscript. N.V. generated tagged Notch flies. L.C. carried out all genetic and cell biology experiments and contributed to imaging.

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Correspondence to Nicolas Vodovar or François Schweisguth.

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The authors declare no competing financial interests.

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Couturier, L., Vodovar, N. & Schweisguth, F. Endocytosis by Numb breaks Notch symmetry at cytokinesis. Nat Cell Biol 14, 131–139 (2012). https://doi.org/10.1038/ncb2419

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