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DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila

Abstract

The Drosophila protein Bazooka is required for both apical–basal polarity in epithelial cells and directing asymmetric cell division in neuroblasts. Here we show that the PDZ-domain protein DmPAR-6 cooperates with Bazooka for both of these functions. DmPAR-6 colocalizes with Bazooka at the apical cell cortex of epithelial cells and neuroblasts, and binds to Bazooka in vitro . DmPAR-6 localization requires Bazooka, and mislocalization of Bazooka through overexpression redirects DmPAR-6 to ectopic sites of the cell cortex. In the absence of DmPAR-6, Bazooka fails to localize apically in neuroblasts and epithelial cells, and is distributed in the cytoplasm instead. Epithelial cells lose their apical–basal polarity in DmPAR-6 mutants, asymmetric cell divisions in neuroblasts are misorientated, and the proteins Numb and Miranda do not segregate correctly into the basal daughter cell. Bazooka and DmPAR-6 are Drosophila homologues of proteins that direct asymmetric cell division in early Caenorhabditis elegans embryos, and our results indicate that homologous protein machineries may direct this process in worms and flies.

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Figure 1: Expression and apical localization of DmPAR-6 in epithelial cells.
Figure 2: DmPAR-6 localizes apically in neuroblasts and binds to Bazooka.
Figure 3: Function of bazooka and inscuteable in DmPAR-6 localization.
Figure 4: Defects in epithelial polarity in DmPAR-6 mutants.
Figure 5: Defects in Bazooka and Inscuteable localization in DmPAR-6 mutants.
Figure 6: Defects in Numb and Miranda localization in DmPAR-6 mutants.

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Acknowledgements

We want to thank M. Glotzer and A. Wodarz for discussion; K. Kemphues and T. Pawson for communicating results before publication; M. Glotzer for comments on the manuscript; and A. Wodarz, B. Chia, Y. N. Jan, D. St Johnston, the Developmental Studies Hybridoma Bank (DSHB) and the Bloomington Drosophila Stock Center for providing antibodies and flystocks.

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Correspondence to Juergen A. Knoblich.

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Petronczki, M., Knoblich, J. DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat Cell Biol 3, 43–49 (2001). https://doi.org/10.1038/35050550

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