Ohshiro T, Yagami T, Zhang C, Matsuzaki F
CREST, Japan Science and Technology Corporation, Sendai.
Nature. 2000 Nov 30;408(6812):593-6. doi: 10.1038/35046087.
Cellular diversity during development arises in part from asymmetric divisions, which generate two distinct cells by transmitting localized determinants from a progenitor cell into one daughter cell. In Drosophila, neuroblasts undergo typical asymmetric divisions to produce another neuroblast and a ganglion mother cell. At mitosis, neural fate determinants, including Prospero and Numb, localize to the basal cortex, from which the ganglion mother cell buds off; Inscuteable and Bazooka, which regulate spindle orientation, localize apically. Here we show that a tumour-suppressor protein, Lethal giant larvae (Lgl), is essential for asymmetric cortical localization of all basal determinants in mitotic neuroblasts, and is therefore indispensable for neural fate decisions. Lgl, which itself is uniformly cortical, interacts with several types of Myosin to localize the determinants. Another tumour-suppressor protein, Lethal discs large (Dlg), participates in this process by regulating the localization of Lgl. The localization of the apical components is unaffected in lgl or dlg mutants. Thus, Lgl and Dlg act in a common process that differentially mediates cortical protein targeting in mitotic neuroblasts, and that creates intrinsic differences between daughter cells.
发育过程中的细胞多样性部分源于不对称分裂，这种分裂通过将局部决定因子从祖细胞传递到一个子细胞中，产生两个不同的细胞。在果蝇中，神经母细胞经历典型的不对称分裂，产生另一个神经母细胞和一个神经节母细胞。在有丝分裂时，包括Prospero和Numb在内的神经命运决定因子定位于基皮层，神经节母细胞从该部位出芽；调节纺锤体取向的Inscuteable和Bazooka定位于顶端。我们在此表明，一种肿瘤抑制蛋白，即致死性巨幼虫（Lgl），对于有丝分裂神经母细胞中所有基底决定因子的不对称皮层定位至关重要，因此对于神经命运决定不可或缺。本身均匀分布于皮层的Lgl与几种类型的肌球蛋白相互作用，以使决定因子定位。另一种肿瘤抑制蛋白，即致死性盘大（Dlg），通过调节Lgl的定位参与这一过程。在lgl或dlg突变体中，顶端成分的定位不受影响。因此，Lgl和Dlg在一个共同的过程中发挥作用，该过程差异性地介导有丝分裂神经母细胞中皮层蛋白的靶向定位，并在子细胞之间产生内在差异。
