Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts

• Published in: Nature (London) 1999-12, Vol.402 (6761), p.548-551
• Main Authors: Knoblich, Juergen A, Schober, Markus, Schaefer, Matthias
• Format: Article
• Language: English
• Subjects: Animals; Bazooka protein; Biological and medical sciences; Carrier Proteins - physiology; Cell Cycle Proteins - physiology; Cell Differentiation - physiology; Cell division; Cell Division - physiology; Cell Movement; Cell Polarity; Classical genetics, quantitative genetics, hybrids; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - physiology; Drosophila; Drosophila - embryology; Drosophila - genetics; Drosophila - physiology; Drosophila Proteins; Embryos; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humanities and Social Sciences; Inscuteable protein; Insect Proteins - physiology; Insects; Intracellular Signaling Peptides and Proteins; Invertebrata; Juvenile Hormones - physiology; letter; Miranda protein; Molecular biology; multidisciplinary; Mutation; Neurons - physiology; Neuropeptides; Numb protein; Precipitin Tests; Protein Binding; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/990135

Asymmetric cell divisions can be generated by the segregation of determinants into one of the two daughter cells. In Drosophila, neuroblasts divide asymmetrically along the apical-basal axis shortly after their delamination from the neuroectodermal epithelium. Several proteins, including Numb and Miranda, segregate into the basal daughter cell and are needed for the determination of its correct cell fate. Both the apical-basal orientation of the mitotic spindle and the localization of Numb and Miranda to the basal cell cortex are directed by Inscuteable, a protein that localizes to the apical cell cortex before and during neuroblast mitosis. Here we show that the apical localizaton of Inscuteable requires Bazooka, a protein containing a PDZ domain that is essential for apical-basal polarity in epithelial cells. Bazooka localizes with Inscuteable in neuroblasts and binds to the Inscuteable localization domain in vitro and in vivo. In embryos lacking both maternal and zygotic bazooka function, Inscuteable no longer localizes asymmetrically in neuroblasts and is instead uniformly distributed in the cytoplasm. Mitotic spindles in neuroblasts are misoriented in these embryos, and the proteins Numb and Miranda fail to localize asymmetrically in metaphase. Our results suggest that direct binding to Bazooka mediates the asymmetric localization of Inscuteable and connects the asymmetric division of neuroblasts to the axis of epithelial apical-basal polarity.