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Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis

Nature Cell Biology volume 9, pages 57–63 (2007)Cite this article

Abstract

Morphogens are secreted signalling molecules that govern many developmental processes1. In the Drosophila wing disc, the transforming growth factor β (TGFβ) homologue Decapentaplegic (Dpp) forms a smooth gradient and specifies cell fate by conferring a defined value of morphogen activity. Thus, neighbouring cells have similar amounts of Dpp protein, and if a sharp discontinuity in Dpp activity is generated between these cells, Jun kinase (JNK)-dependent apoptosis is triggered to restore graded positional information2,3. To date, it has been assumed that this apoptotic process is only activated when normal signalling is distorted. However, we now show that a similar process occurs during normal development: rupture in Dpp activity occurs during normal segmentation of the distal legs of Drosophila. This sharp boundary of Dpp signalling, independently of the absolute level of Dpp activity, induces a JNK—reaper-dependent apoptosis required for the morphogenesis of a particular structure of the leg, the joint. Our results show that Dpp could induce a developmental programme not only in a concentration dependent manner, but also by the creation of a sharp boundary of Dpp activity. Furthermore, the same process could be used either to restore a normal pattern in response to artificial disturbance or to direct a morphogenetic process.

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Figure 1: Programmed cell death occurs at the presumptive joints.
Figure 2: Distal joint morphogenesis requires apoptosis.
Figure 3: Dpp, P-Mad and rpr–lacZ expression patterns in third instar and prepupal leg discs.
Figure 4: Apoptosis induction and joint formation require a sharp boundary of Dpp signalling.
Figure 5: Schematic representation of a model of joint formation in distal leg segments.

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Acknowledgements

We thank: G. Morata for his help, support and comments on the manuscript; J. F. de Celis, S. Noselli and M. Lemonnier for their comments on the manuscript; K. Basler, S. Baumgartner, J. F. De Celis, A. Macías, G. Morata, S. Noselli, T. Tabata, C. S. Thummel and the Bloomington Stock Center for stocks and reagents; N. Azpiazu, J. Casanova and M. Milán for providing space and laboratory facilities; S. Aldaz for pointing out the reaper expression in the leg discs; H. Herranz for providing the dpp probe; F. A. Martín for discussions; and R. González and the personnel of the electronic microscopy facility at the CBMSO for technical assistance. This work has been supported by grants from the Dirección General de Investigación Científica y Técnica (BMC 2002-00300), the Comunidad Autónoma de Madrid (08.1/0031/2001.1 and GR/SAL/0147/2004) and an Institutional Grant from the Fundación Ramón Areces. C.M. is a recipient of a Formación del Personal Universitario (F.P.U.) fellowship from the Ministerio de Educación y Ciencia.

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  1. Magali Suzanne

    Present address: Institute of Signaling, Developmental Biology and Cancer, UMR6543/CNRS, Université Nice Sophia-Antipolis, Parc Valrose, 06108, Nice Cedex, France

Authors and Affiliations

  1. Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, 28 049, Madrid, Spain

    Cristina Manjón, Ernesto Sánchez-Herrero & Magali Suzanne

Authors
  1. Cristina Manjón
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Contributions

C.M. carried out experimental work, E.S. designed experiments and wrote the manuscript and M.S. carried out experimental research, designed experiments and wrote the manuscript.

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Correspondence to Magali Suzanne.

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The authors declare no competing financial interests.

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Supplementary figures S1, S2, S3 and Supplementary table S1 (PDF 544 kb)

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Manjón, C., Sánchez-Herrero, E. & Suzanne, M. Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis. Nat Cell Biol 9, 57–63 (2007). https://doi.org/10.1038/ncb1518

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