Letter | Published:

Nanotubes mediate niche–stem-cell signalling in the Drosophila testis

Nature volume 523, pages 329332 (16 July 2015) | Download Citation

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Abstract

Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short range such that only stem cells but not their differentiating progeny receive the self-renewing signals1. However, the cellular mechanisms that limit niche signalling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells form previously unrecognized structures, microtubule-based nanotubes, which extend into the hub, a major niche component. Microtubule-based nanotubes are observed specifically within germline stem cell populations, and require intraflagellar transport proteins for their formation. The bone morphogenetic protein (BMP) receptor Tkv localizes to microtubule-based nanotubes. Perturbation of microtubule-based nanotubes compromises activation of Dpp signalling within germline stem cells, leading to germline stem cell loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for microtubule-based nanotube formation. We propose that microtubule-based nanotubes provide a novel mechanism for selective receptor–ligand interaction, contributing to the short-range nature of niche–stem-cell signalling.

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Acknowledgements

We thank T. Kornberg, S. Roy, T. Avidor-Reiss, E. Laufer, A. Rodal, D. Sharp, S. Noselli, A. C. Spradling, T. E. Haerry, E. R. Gavis, C.-Y. Lee, T. Xie, B. McCabe, K. S. McKim, Bloomington Drosophila Stock Center, Vienna Drosophila Resource Center and the Developmental Studies Hybridoma Bank for reagents; S. Roy, T. Kornberg, G. Boekhoff-Falk and D. King for comments and advice; K. Luby-Phelps, A. Bugde and M. Acar for advice for imaging/image data processing; and the Yamashita and Buszczak laboratory members for discussion. The research in the Yamashita laboratory is supported by the Howard Hughes Medical Institute. Y.M.Y. is supported by the MacArthur Foundation.

Author information

Affiliations

  1. Life Sciences Institute, Department of Cell and Developmental Biology Medical School, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Mayu Inaba
    •  & Yukiko M. Yamashita
  2. Howard Hughes Medical Institute, University of Michigan Ann Arbor, Michigan 48109, USA

    • Mayu Inaba
    •  & Yukiko M. Yamashita
  3. Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA

    • Mayu Inaba
    •  & Michael Buszczak

Authors

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Contributions

M.I. conceived the project, and executed experiments. All authors designed experiments, analysed the data, and wrote and edited the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Michael Buszczak or Yukiko M. Yamashita.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Notes 1-2 and Supplementary Table 1.

Videos

  1. 1.

    A representative video of GSC division visualized by GFP-αTub.

    GSC in anaphase at 0 min undergoes cell division and grows a MT-nanotube from GSC-hub interface into the hub area (see Extended Data Fig. 1e).

  2. 2.

    A representative video of interphase MT-nanotubes visualized by GFP-αTub.

    A representative video of interphase MT-nanotubes visualized by GFP-αTub.

  3. 3.

    Spatial relationships between MT-nanotubes and hub cell junctions.

    3d rendering shows that the MT-nanotubes invaginate into a hub cell. A GSC with an MT-nanotube (GFP-αTub, green) Hub-GSC junction and hub cell coltex (Arm staining, red).

  4. 4.

    Membrane lipids around a MT-nanotube.

    GFP-αTub (green). FM4-64 Lipophilic Styryl Dye (magenta) shows that the MT-nanotubes are surrounded by membrane.

  5. 5.

    A video of oblique sectioning of an MT-nanotube.

    Membrane (magenta) components ensheath a MT-nanotube (green).

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DOI

https://doi.org/10.1038/nature14602

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