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Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing

Nature volume 394, pages 82–84 (1998)Cite this article

Abstract

In developing organs, the regulation of cell proliferation and patterning of cell fates is coordinated. How this coordination is achieved, however, is unknown. In the developing Drosophila wing, both cell proliferation and patterning require the secreted morphogen Wingless (Wg) at the dorsoventral compartment boundary (reviewed in ref. 1). Late in wing development, Wg also induces a zone of non-proliferating cells at the dorsoventral boundary. This zone gives rise to sensory bristles of the adult wing margin2,3. Here we investigate how Wg coordinates the cell cycle with patterning by studying the regulation of this growth arrest. We show that Wg, in conjunction with Notch, induces arrest in both the G1 and G2 phases of the cell cycle in separate subdomains of the zone of non-proliferating cells. Wg induces G2 arrest in two subdomains by inducing the proneural genes achaete and scute, which downregulate the mitosis-inducing phosphatase String (Cdc25)4. Notch activity creates a third domain by preventing arrest at G2 in wg-expressing cells, resulting in their arrest in G1.

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Figure 1: The ZNC contains cells arrested in G1 or G2 phase.
Figure 2: Wg regulates stg in the G2-arrested cells.
Figure 3: Ac and Sc repress stg transcription.
Figure 4: Notch activity prevents G2 arrest.
Figure 5: Model of cell-cycle arrests in the ZNC.

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Acknowledgements

We thank T. Neufeld, A. Bejsovec, M. Peifer, J-P. Vincent, C. Doe, S. Blair, S. Carroll, R. Nusse, S. Parkhurst, H. Richardson, C. Lehner, G. Boulianne and E. Giniger for gifts of flies or antibodies, C. Queva and K. Sharma for communicating unpublished results, and R. Kopan, M. Schubiger, S. Blair, J. Overbaugh, J. Priess, M. Emerman, J. Roberts and members of the Edgar lab for discussions and comments on the manuscript. L.A.J. is supported by a grant from the NIH. B.A.E. receives support from the NIH, and is a Rita Allen and a Lucille P. Markey Scholar.

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  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, 98109, Washington, USA

    Laura A. Johnston & Bruce A. Edgar

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  1. Laura A. Johnston
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  2. Bruce A. Edgar
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Correspondence to Laura A. Johnston.

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Johnston, L., Edgar, B. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature 394, 82–84 (1998). https://doi.org/10.1038/27925

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