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Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast

Nature volume 408, pages 593–596 (2000)Cite this article

Abstract

Cellular diversity during development arises in part from asymmetric divisions, which generate two distinct cells by transmitting localized determinants from a progenitor cell into one daughter cell. In Drosophila, neuroblasts undergo typical asymmetric divisions to produce another neuroblast and a ganglion mother cell1,2. At mitosis, neural fate determinants, including Prospero and Numb, localize to the basal cortex3,4, from which the ganglion mother cell buds off; Inscuteable and Bazooka, which regulate spindle orientation, localize apically5,6,7,8. Here we show that a tumour-suppressor protein, Lethal giant larvae (Lgl)9, is essential for asymmetric cortical localization of all basal determinants in mitotic neuroblasts, and is therefore indispensable for neural fate decisions. Lgl, which itself is uniformly cortical, interacts with several types of Myosin to localize the determinants. Another tumour-suppressor protein, Lethal discs large (Dlg)10, participates in this process by regulating the localization of Lgl. The localization of the apical components is unaffected in lgl or dlg mutants. Thus, Lgl and Dlg act in a common process that differentially mediates cortical protein targeting in mitotic neuroblasts, and that creates intrinsic differences between daughter cells.

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Figure 1: Miranda and Numb but not Baz mislocalize in mitotic neuroblasts of lgl and dlg mutant embryos.
Figure 2: Localization of Lgl and Dlg in neuroblasts.
Figure 3: Requirement for Lgl early during mitosis and interactions with Myosins in Miranda localization.
Figure 4: Cell-fate transformation in the external sensory organ lineage induced by a reduction in lgl activity.

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Acknowledgements

We thank A. Brand, P. Bryant, W. Chia, D. Glover, S. Hayashi, Y.N. Jan, E. Knust, C. Peng, F. Schweisguth, M. Semeriva, A. Shearn, J. Skeath, Umea Drosophila Stock Center and Bloomington Drosophila Stock Center for providing flies and reagents; K. Hisata for technical assistance; N. Fuse, Y. Izumi, A. Sehara-Fujisawa and W. Chia for comments on the manuscript. We also thank C. Peng and C. Doe for communicating unpublished results; we are indebted to them for first observing Miranda in lgl–zip double mutants. This work was supported (through F.M.) by grants-in-aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan, and by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation.

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Authors and Affiliations

  1. CREST, Japan Science and Technology Corporation,

    Tomokazu Ohshiro, Takako Yagami, Chuan Zhang & Fumio Matsuzaki

  2. Cell Asymmetry Group, RIKEN Center for Developmental Biology,

    Fumio Matsuzaki

  3. Department of Developmental Neurobiology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai, 980-8575, Japan

    Tomokazu Ohshiro, Chuan Zhang & Fumio Matsuzaki

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  1. Tomokazu Ohshiro
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Correspondence to Fumio Matsuzaki.

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Ohshiro, T., Yagami, T., Zhang, C. et al. Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408, 593–596 (2000). https://doi.org/10.1038/35046087

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