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Local caspase activity directs engulfment of dendrites during pruning

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Abstract

Pruning is important for sculpting neural circuits, as it removes excessive or inaccurate projections. Here we show that the removal of sensory neuron dendrites during pruning in Drosophila melanogaster is directed by local caspase activity. Suppressing caspase activity prevented dendrite removal, whereas a global activation of caspases within a neuron caused cell death. A new genetically encoded caspase probe revealed that caspase activity is confined to the degenerating dendrites of pruning neurons.

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Figure 1: Disrupting apoptotic machinery suppresses dendrite pruning.
Figure 2: The genetically encoded caspase reporter CD8::PARP::Venus reveals local caspase activity in dendrites of pruning da neurons.
Figure 3: Relationship between phagocytic activity, branch severing and caspase activation.

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Acknowledgements

We thank M. Schubiger for helpful discussions; T. Awasaki for informing us about the second site mutation on the draperΔ5 chromosome; E. Baehrecke (University of Maryland Biotechnology Institute, College Park, Maryland), S. Kumar (Hanson Institute and Institute of Medical and Veterinary Science Adelaide, Australia), P. Meier (Institute of Cancer Research, London), W. Grueber (Columbia University, New York), J. Abrams (University of Texas/Southwestern Medical Center, Dallas), W. Johnson (University of Iowa, Iowa City, Iowa), G. Schubiger and S. McNabb (University of Washington, Seattle), M. Freeman (University of Massachusetts Medical School, Worcester, Massachusetts) and the Bloomington Drosophila Stock Center at Indiana University for fly stocks; A. Miyawaki (RIKEN Brain Science Institute, Saitama, Japan) for plasmids; and S. Lennox for technical assistance. Research was supported by grants from the US National Institutes of Health (NS-029971), the Medical Research Council and the CREST program of the Japan Science and Technology Agency.

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Authors and Affiliations

  1. MRC Centre for Developmental Neurobiology, King's College London, London, SE1 1UL, UK

    Darren W Williams & Agnieszka Krzyzanowska

  2. Department of Biology, University of Washington, Seattle, 98195, Washington, USA

    Darren W Williams & James W Truman

  3. Department of Developmental Genetics, National Institute of Genetics, Mishima, 411-8540, Shizuoka, Japan

    Shu Kondo & Yasushi Hiromi

  4. CREST, Japan Science and Technology Agency, National Institute of Genetics, Mishima, 411-8540, Shizuoka, Japan

    Shu Kondo & Yasushi Hiromi

  5. Department of Genetics, SOKENDAI, Mishima, 411-8540, Shizuoka, Japan

    Shu Kondo & Yasushi Hiromi

  6. Division of Morphology and Organogenesis, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, 105-8461, Japan

    Shu Kondo

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  1. Darren W Williams
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  2. Shu Kondo
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  3. Agnieszka Krzyzanowska
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  4. Yasushi Hiromi
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  5. James W Truman
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Contributions

D.W.W. designed the study, conducted the experimental work, interpreted the data and wrote the manuscript. A.K. generated the adult viable draperΔ5 chromosome and assisted with experimental work. S.K. designed and built the caspase probe, helped interpret data and assisted in writing the manuscript. Y.H. and J.W.T. contributed to experimental design, data interpretation and writing of the manuscript.

Corresponding author

Correspondence to Darren W Williams.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

The dendrites of ddaC are pruned by local degeneration. (PDF 632 kb)

Supplementary Fig. 2

The role of caspase activity in ddaC pruning. (PDF 646 kb)

Supplementary Methods (PDF 131 kb)

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Williams, D., Kondo, S., Krzyzanowska, A. et al. Local caspase activity directs engulfment of dendrites during pruning. Nat Neurosci 9, 1234–1236 (2006). https://doi.org/10.1038/nn1774

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  • DOI: https://doi.org/10.1038/nn1774

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