Article | Published:

A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning

Nature Neuroscience volume 12, pages 14971505 (2009) | Download Citation

Abstract

Pruning that selectively eliminates neuronal processes is crucial for the refinement of neural circuits during development. In Drosophila, the class IV dendritic arborization neuron (ddaC) undergoes pruning to remove its larval dendrites during metamorphosis. We identified Sox14 as a transcription factor that was necessary and sufficient to mediate dendrite severing during pruning in response to ecdysone signaling. We found that Sox14 mediated dendrite pruning by directly regulating the expression of the target gene mical. mical encodes a large cytosolic protein with multiple domains that are known to associate with cytoskeletal components. mical mutants had marked severing defects during dendrite pruning that were similar to those of sox14 mutants. Overexpression of Mical could significantly rescue pruning defects in sox14 mutants, suggesting that Mical is a major downstream target of Sox14 during pruning. Thus, our findings indicate that a previously unknown pathway composed of Sox14 and its cytoskeletal target Mical governs dendrite severing.

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Acknowledgements

We thank H. Aberle, R. Barrio, Y.N. Jan, W.A. Johnson, the Bloomington Stock Center, Developmental Studies Hybridoma Bank (University of Iowa) and Vienna Drosophila RNAi Center for generously providing antibodies and fly stocks. We thank members of the Yu and Wang laboratories for stimulating discussions and Z.L. Ong for technical assistance. We thank W. Chia, S. Cohen, P. Rorth, S. Roy, J. Varghese and G. Feng for helpful discussions and for reading the manuscript. This work was supported by Temasek Life Sciences Laboratory (F.Y.), Duke–National University of Singapore (MOE2008-T2-1-048 and NRF-RF2009-02 to H.W.), and grants from the US National Institutes of Health and the National Institute of Neurological Disorders and Stroke (RO1NS35165) and the Howard Hughes Medical Institute (A.L.K.). D.K. is supported by the Singapore Millennium Foundation.

Author information

Author notes

    • Daniel Kirilly
    •  & Ying Gu

    These authors contributed equally to this work.

Affiliations

  1. Temasek Life Sciences Laboratory, National University of Singapore, Singapore.

    • Daniel Kirilly
    • , Ying Gu
    • , Yafen Huang
    •  & Fengwei Yu
  2. Department of Biological Sciences, National University of Singapore, Singapore.

    • Ying Gu
    • , Boon Chuan Low
    •  & Fengwei Yu
  3. Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

    • Zhuhao Wu
    •  & Alex L Kolodkin
  4. Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin, USA.

    • Arash Bashirullah
  5. Neuroscience and Behavioral Disorder Program, Duke–National University of Singapore Graduate Medical School Singapore, Singapore.

    • Hongyan Wang
    •  & Fengwei Yu
  6. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • Hongyan Wang

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Contributions

D.K. and Y.G. conducted the majority of the experiments and data analysis on sox14 and mical, respectively. Y.H. contributed to the biochemical experiments. Z.W. and A.L.K. provided reagents for mical. A.B. provided the pupal lethal mutant collection. B.C.L. and F.Y. cosupervised Y.G. F.Y. and H.W. conceptualized and designed the study. F.Y. supervised the project. D.K., H.W. and F.Y. wrote the manuscript.

Corresponding author

Correspondence to Fengwei Yu.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–12

Videos

  1. 1.

    Supplementary Movie 1

    The dynamics of dendrite removal in a ddaC neuron. Confocal time-lapse movie of a wt ppk-GAL4>mCD8GFP labelled ddaC neuron between 4 and 13 h APF. Frames were recorded every 6 minutes.

  2. 2.

    Supplementary Movie 2

    Dendritic pruning is blocked in sox14Δ13 homozygotes. Confocal time-lapse movie of a ppk-GAL4>mCD8GFP labelled ddaC derived from a sox14Δ13 mutant pupa between 6 and 10 h APF. No severing or blebbing occurs in sox14 mutants during this period. Frames were recorded every 5 minutes.

  3. 3.

    Supplementary Movie 3

    Dendrites of ddaCs are persisting drastically longer in mical15256 homozygotes. Confocal time-lapse recording of a mical15256 homozygous pupa, in which ddaCs are labelled by ppk-EGFP. Frames are recorded from 11 to 17 h APF with 5 minutes intervals.

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DOI

https://doi.org/10.1038/nn.2415

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