Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast

Cellular diversity during development arises in part from asymmetric divisi ons, which generate two distinct cells by transmitting localized determinan ts from a progenitor cell into one daughter cell. In Drosophila, neuroblast s undergo typical asymmetric divisions to produce another neuroblast and a ganglion mother cell(1,2). At mitosis, neural fate determinants, including Prospero and Numb, localize to the basal cortex(3,4), from which the gangli on mother cell buds off; Inscuteable and Bazooka, which regulate spindle or ientation, localize apically(5-8). Here we show that a tumour-suppressor pr otein, Lethal giant larvae (Lgl)(9), is essential for asymmetric cortical l ocalization of all basal determinants in mitotic neuroblasts, and is theref ore indispensable for neural fate decisions. Lgl, which itself is uniformly cortical, interacts with several types of Myosin to localize the determina nts. Another tumour-suppressor protein, Lethal discs large (Dlg)(10), parti cipates in this process by regulating the localization of Lgl. The localiza tion of the apical components is unaffected in lgl or dlg mutants. Thus, Lg l and Dlg act in a common process that differentially mediates cortical pro tein targeting in mitotic neuroblasts, and that creates intrinsic differenc es between daughter cells.