Abstract
Asymmetric cell division is important in generating cell diversity from bacteria to mammals. Drosophila melanogaster neuroblasts are a useful model system for investigating asymmetric cell division because they establish distinct apical–basal cortical domains, have an asymmetric mitotic spindle aligned along the apical–basal axis, and divide unequally to produce a large apical neuroblast and a small basal daughter cell (GMC)1,2. Here we show that Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl) tumour suppressor proteins regulate multiple aspects of neuroblast asymmetric cell division. Dlg/Scrib/Lgl proteins show apical cortical enrichment at prophase/metaphase, and then have a uniform cortical distribution. Mutants have defects in basal protein targeting, a reduced apical cortical domain and reduced apical spindle size. Defects in apical cell and spindle pole size result in symmetric or inverted neuroblast cell divisions. Inverted divisions correlate with the appearance of abnormally small neuroblasts and large GMCs, showing that neuroblast/GMC identity is more tightly linked to cortical determinants than cell size. We conclude that Dlg/Scrib/Lgl are important in regulating cortical polarity, cell size asymmetry and mitotic spindle asymmetry in Drosophila neuroblasts.
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Acknowledgements
We thank D. Bilder for providing scrib1 germ line clones and DNA, B. Chia, V. Budnik, D. St Johnston, H. Vaessin, C. Goodman and M. Kuroda for fly stocks and antibodies, S, Siegrist for Dlg–GFP movies and Fig. 1t, and K. Siller, S. Siegrist, Z. E. Gomes, H.-. Shih, M. Rolls and B. Bowerman for comments. This work was funded by National Institutes of Health grants GM58899, and the Howard Hughes Medical Institute, in which C.Q.D. is an Investigator.
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Supplementary Movie 1
Dlg::GFP shows dynamic apical enrichment adjacent to the apical spindle pole during metaphase in living embryonic neuroblasts. Dlg::GFP and the microtubule-binding protein Zeus::GFP are imaged in a lateral view of a stage 11 embryo. The apical neuroblast cortex is indicated with white arrowheads during mitosis. 180X accelerated. (MOV 2079 kb)
Supplementary Figures
Figure S1 Quantitation of apical/basal cell size ratios in wild type and mutant neuroblasts. (PDF 756 kb)
Figure S3 Quantitation of centrosome and spindle asymmetry in wild type and mutant neuroblasts.
Description of Supplementary Movie 1.
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Albertson, R., Doe, C. Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nat Cell Biol 5, 166–170 (2003). https://doi.org/10.1038/ncb922
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DOI: https://doi.org/10.1038/ncb922
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