Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts

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Abstract

Asymmetric cell division generates daughter cells with different developmental fates from progenitor cells that contain localized determinants. During this division, the asymmetric localization of cell-fate determinants and the orientation of the mitotic spindle must be precisely coordinated. In Drosophila neuroblasts, inscuteable controls both spindle orientation and the asymmetric localization of the cell-fate determinants Prospero and Numb1. Inscuteable itself is localized in an apical cortical crescent and thus reflects the intrinsic asymmetry of the neuroblast1,2. Here we show that localization of Inscuteable depends on Bazooka, a protein containing three PDZ domains with overall sequence similarity to Par-3 of Caenorhabditis elegans3. Bazooka and Inscuteable form a complex that also contains Staufen, a protein responsible for the asymmetric localization of prospero messenger RNA. We propose that, after delamination of the neuroblast from the neuroepithelium, Bazooka provides an asymmetric cue in the apical cytocortex that is required to anchor Inscuteable. As Bazooka is also responsible for the maintenance of apical–basal polarity in epithelial tissues4, it may be the missing link between epithelial polarity and neuroblast polarity.

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Figure 1: Baz and Insc colocalize in neuroblasts.
Figure 2: Baz is necessary and sufficient for cortical localization of Insc.
Figure 3: The subcellular localization of Pros is abnormal in baz mutant embryos.
Figure 4: Cortical localization of Insc depends on Baz in S2 cells.
Figure 5: Baz, Insc and Stau are associated in a complex.

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Acknowledgements

We thank B. Chia, R. Kraut, D. St Johnston and C. Doe for antibodies; A. Müller and E. Wieschaus for bazXi106 FRT 18D flies; D. St Johnston for mat67G4 flies; and J. Campos-Ortega for Insc cDNA. F. Grawe, M. Müller-Borg and A. Grimm provided technical assistance. We also thank J. Campos-Ortega, A. Müller, O. Bossinger, K. Johnson and P. Hardy for critical reading of the manuscript, and J. Knoblich for communication of results before publication. This work was supported by grants from the Deutsche Forschungsgemeinschaft.

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Correspondence to Andreas Wodarz.

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Wodarz, A., Ramrath, A., Kuchinke, U. et al. Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Nature 402, 544–547 (1999) doi:10.1038/990128

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