Hughes Julian R, Bullock Simon L, Ish-Horowicz David
Developmental Genetics Laboratory, Cancer Research UK, Post Office Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Curr Biol. 2004 Nov 9;14(21):1950-6. doi: 10.1016/j.cub.2004.10.022.
Drosophila neuroblasts undergo asymmetric divisions along the apicobasal axis to produce two daughter cells of unequal size and different developmental fate. Inscuteable (Insc) protein functions as part of an apically localized complex to coordinate orientation of the mitotic spindle and basal sorting of cell fate determinants. insc mRNA transcripts also localize apically in neuroblasts, yet the mechanism underpinning this process and its developmental significance are unknown. Here, we show that the Egalitarian (Egl)/Bicaudal-D (BicD)/dynein mRNA transport machinery mediates apical localization of insc mRNA transcripts in neuroblasts, and we provide evidence that insc localization is required for efficient apical targeting of Insc protein. egl and BicD mutant neuroblasts display defects in apicobasal polarity, which is consistent with apical Insc activity being reduced. Also, we observe shortened mitotic spindles at metaphase in egl, BicD, and insc mutant neuroblasts and demonstrate a previously unknown, dose-dependent requirement for Insc in augmenting metaphase spindle length. We conclude that localization of insc mRNA transcripts in neuroblasts confers maximal levels of apical Insc activity, which is required for accurate control of metaphase spindle length, division orientation, and asymmetric cell division.
果蝇神经母细胞沿顶-基轴进行不对称分裂，产生两个大小不等、发育命运不同的子细胞。无翅（Insc）蛋白作为顶端定位复合物的一部分发挥作用，以协调有丝分裂纺锤体的定向和细胞命运决定因子的基部分选。Insc mRNA转录本也定位于神经母细胞的顶端，但支撑这一过程的机制及其发育意义尚不清楚。在这里，我们表明，均等（Egl）/双尾-D（BicD）/动力蛋白mRNA转运机制介导Insc mRNA转录本在神经母细胞中的顶端定位，并且我们提供证据表明Insc定位是Insc蛋白有效顶端靶向所必需的。Egl和BicD突变的神经母细胞在顶-基极性上表现出缺陷，这与顶端Insc活性降低一致。此外，我们在Egl、BicD和Insc突变的神经母细胞中期观察到有丝分裂纺锤体缩短，并证明了Insc在增加中期纺锤体长度方面以前未知的剂量依赖性需求。我们得出结论，Insc mRNA转录本在神经母细胞中的定位赋予了顶端Insc活性的最大水平，这对于精确控制中期纺锤体长度、分裂方向和不对称细胞分裂是必需的。
