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The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts

Nature Cell Biology volume 8, pages 594–600 (2006)Cite this article

Abstract

Asymmetric cell division generates cell diversity during development1,2 and regulates stem-cell self-renewal in Drosophila and mammals3,4. In Drosophila, neuroblasts align their spindle with a cortical Partner of Inscuteable (Pins)–Gαi crescent to divide asymmetrically, but the link between cortical polarity and the mitotic spindle is poorly understood. Here, we show that Pins directly binds, and coimmunoprecipitates with, the NuMA-related Mushroom body defect (Mud) protein. Pins recruits Mud to the neuroblast apical cortex, and Mud is also strongly localized to centrosome/spindle poles, in a similar way to NuMA. In mud mutants, cortical polarity is normal, but the metaphase spindle frequently fails to align with the cortical polarity axis. When spindle orientation is orthogonal to cell polarity, symmetric division occurs. We propose that Mud is a functional orthologue of mammalian NuMA and Caenorhabditis elegans Lin-5, and that Mud coordinates spindle orientation with cortical polarity to promote asymmetric cell division.

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Figure 1: Drosophila Mud protein domains and interaction with Pins.
Figure 2: Mud is localized to the cortex, spindle poles and spindle microtubules.
Figure 3: Pins recruits Mud to the neuroblast apical cortex.
Figure 4: Mud is required for spindle orientation in metaphase neuroblasts.
Figure 5: Mud aligns the centrosome/spindle poles with cortical polarity.

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Acknowledgements

We would especially like to thank H. Nash for providing Mud antibody and mutants ahead of publication, and for sharing unpublished data. We also thank F. Matsuzaki for communicating results prior to publication; R. Nipper, K. Prehoda, T. Kaufman, T. Megraw, F. Yu, X. Morin, W. Chia and A. Wodarz for generously sharing reagents; S. Siegrist for providing in vitro cultures of embryonic neuroblasts; S. Schneider for his help with sequence alignments; K. Hirono and K. Robinson for excellent technical assistance; and S. Siegrist, B. Bowerman, K. Prehoda and S. Schneider for stimulating discussions. This work was supported by an American Heart Association pre-doctoral fellowship (K.H.S.) and by the Howard Hughes Medical Institute (C.Q.D).

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  1. Institute of Molecular Biology, Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA

    Karsten H. Siller, Clemens Cabernard & Chris Q. Doe

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  1. Karsten H. Siller
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Correspondence to Chris Q. Doe.

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Siller, K., Cabernard, C. & Doe, C. The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nat Cell Biol 8, 594–600 (2006). https://doi.org/10.1038/ncb1412

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