Rose L S, Kemphues K
Section of Genetics and Development, Cornell University, Ithaca, NY 14853, USA.
Development. 1998 Apr;125(7):1337-46. doi: 10.1242/dev.125.7.1337.
The orientation of cell division is a critical aspect of development. In 2-cell C. elegans embryos, the spindle in the posterior cell is aligned along the long axis of the embryo and contributes to the unequal partitioning of cytoplasm, while the spindle in the anterior cell is oriented transverse to the long axis. Differing spindle alignments arise from blastomere-specific rotations of the nuclear-centrosome complex at prophase. We have found that mutations in the maternally expressed gene let-99 affect spindle orientation in all cells during the first three cleavages. During these divisions, the nuclear-centrosome complex appears unstable in position. In addition, in almost half of the mutant embryos, there are reversals of the normal pattern of spindle orientations at second cleavage: the spindle of the anterior cell is aligned with the long axis of the embryo and nuclear rotation fails in the posterior cell causing the spindle to form transverse to the long axis. In most of the remaining embryos, spindles in both cells are transverse at second cleavage. The distributions of several asymmetrically localized proteins, including P granules and PAR-3, are normal in early let-99 embryos, but are perturbed by the abnormal cell division orientations at second cleavage. The accumulation of actin and actin capping protein, which marks the site involved in nuclear rotation in 2-cell wild-type embryos, is abnormal but is not reversed in let-99 mutant embryos. Based on these data, we conclude that let-99(+) is required for the proper orientation of spindles after the establishment of polarity, and we postulate that let-99(+) plays a role in interactions between the astral microtubules and the cortical cytoskeleton.
细胞分裂的方向是发育的一个关键方面。在二细胞期的秀丽隐杆线虫胚胎中，后细胞中的纺锤体沿着胚胎的长轴排列，这有助于细胞质的不均等分配，而前细胞中的纺锤体则垂直于长轴定向。不同的纺锤体排列源于前期核 - 中心体复合体在卵裂球特异性的旋转。我们发现，母源表达基因let - 99的突变会影响前三次卵裂期间所有细胞的纺锤体定向。在这些分裂过程中，核 - 中心体复合体在位置上似乎不稳定。此外，在几乎一半的突变胚胎中，第二次卵裂时纺锤体定向的正常模式发生反转：前细胞的纺锤体与胚胎的长轴对齐，而后细胞中的核旋转失败，导致纺锤体垂直于长轴形成。在其余大多数胚胎中，两个细胞中的纺锤体在第二次卵裂时都是横向的。几种不对称定位的蛋白质，包括P颗粒和PAR - 3，在早期let - 99胚胎中的分布是正常的，但在第二次卵裂时会受到异常细胞分裂方向的干扰。肌动蛋白和肌动蛋白封端蛋白的积累，这在二细胞野生型胚胎中标记了参与核旋转的位点，是异常的，但在let - 99突变胚胎中并没有反转。基于这些数据，我们得出结论，let - 99(+)在极性建立后纺锤体的正确定向中是必需的，并且我们推测let - 99(+)在星体微管与皮质细胞骨架之间的相互作用中发挥作用。
