The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts

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Drosophila neuroblasts are a model system for studying asymmetric cell division: they divide unequally to produce an apical neuroblast and a basal ganglion mother cell that differ in size, mitotic activity and developmental potential. During neuroblast mitosis, an apical protein complex orients the mitotic spindle and targets determinants of cell fate to the basal cortex1, but the mechanism of each process is unknown. Here we show that the tumour-suppressor genes lethal giant larvae (lgl) and discs large (dlg) regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts. Dlg protein is apically enriched and is required for maintaining cortical localization of Lgl protein. Basal protein targeting requires microfilament and myosin function, yet the lgl phenotype is strongly suppressed by reducing levels of myosin II. We conclude that Dlg and Lgl promote, and myosin II inhibits, actomyosin-dependent basal protein targeting in neuroblasts.

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Figure 1: Lgl and Dlg are required for basal protein targeting but not spindle orientation in embryonic neuroblasts.
Figure 2: Lgl and Dlg are required for basal protein targeting in larval brain neuroblasts.
Figure 3: Dlg and Lgl protein localization in neuroblasts.
Figure 4: Myosins negatively and positively regulate basal protein targeting in neuroblasts.


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We thank H. Dou for assistance in the deficiency screen; S, Scheider for phylogenetic analysis of Lgl; S. Siegrist and S. Fuerstenberg for Supplementary Fig. 1a–h; D. Bilder, J. K. Roy and N. Perrimon for sharing unpublished results, the FRT lgl4 chromosome, and some lglGLC embryos; B. Mechler, V. Malhotra, B. Chia, E. Knust, M. Peifer, Y. N. Jan, P. Bryant, C. Logan, R. Nusse and the Bloomington stock centre for providing antibodies or fly stocks; and T. Isshiki, S. Fuerstenberg, B. Bowerman for comments and sharing unpublished data. This work was supported by the NIH and HHMI, of which C.Q.D. is an Associate Investigator.

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Correspondence to Chris Q. Doe.

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