Bazooka is required for polarisation of the Drosophila anterior-posterior axis
Bazooka is required for polarisation of the Drosophila anterior-posterior axis
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DOI：
10.1242/dev.045807
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发表时间：
2010-05-15
期刊：
影响因子：
4.6
通讯作者：
St Johnston, Daniel
中科院分区：
文献类型：
--
作者：
Doerflinger, Helene;Vogt, Nina;St Johnston, Daniel
果蝇的前后轴(AP轴)由第9期卵母细胞的极化以及随后双核和Oskar mRNAs定位于细胞的相反两极决定。卵母细胞的极性被认为取决于在线虫中产生AP极性的相同的PAR蛋白，由Bazooka(Baz；PAR-3)、PAR-6和aPKC组成的复合体标记前侧皮质，PAR-1定义后侧皮质。然而，Baz复合体在卵母细胞极性中的作用仍不清楚，因为尽管Baz缺失突变阻碍了卵母细胞的决定，但逃脱这种早期停滞的卵室通常在第9期形成正常的极性。在这里，我们描述了一个在第9期产生穿透性极性表型而不影响卵母细胞决定的Baz等位基因，表明Baz对于轴的形成是必不可少的。BAZ、PAR-6和PAR-1在卵母细胞中的定位动态表明，轴不像线虫那样因皮质收缩而极化，而是表明卵母细胞的再极化是由蛋白激酶C的后部失活或PAR-1的激活触发的。这种最初的不对称性随后被前部BAZ复合体和后部PAR-1和LGL之间的相互抑制所强化。最后，我们发现，PAR-1中aPKC磷酸化位点的突变导致PAR-1在皮质中的均匀定位和皮质微管的丢失。由于不可磷酸化的PAR-1对不可抑制的BAZ是上位的，PAR-1似乎在其他PAR蛋白的下游起作用，极化卵母细胞微管细胞骨架。
The Drosophila anterior-posterior (AP) axis is determined by the polarisation of the stage 9 oocyte and the subsequent localisation of bicoid and oskar mRNAs to opposite poles of the cell. Oocyte polarity has been proposed to depend on the same PAR proteins that generate AP polarity in C. elegans, with a complex of Bazooka (Baz; Par-3), Par-6 and aPKC marking the anterior and lateral cortex, and Par-1 defining the posterior. The function of the Baz complex in oocyte polarity has remained unclear, however, because although baz-null mutants block oocyte determination, egg chambers that escape this early arrest usually develop normal polarity at stage 9. Here, we characterise a baz allele that produces a penetrant polarity phenotype at stage 9 without affecting oocyte determination, demonstrating that Baz is essential for axis formation. The dynamics of Baz, Par-6 and Par-1 localisation in the oocyte indicate that the axis is not polarised by a cortical contraction as in C. elegans, and instead suggest that repolarisation of the oocyte is triggered by posterior inactivation of aPKC or activation of Par-1. This initial asymmetry is then reinforced by mutual inhibition between the anterior Baz complex and posterior Par-1 and Lgl. Finally, we show that mutation of the aPKC phosphorylation site in Par-1 results in the uniform cortical localisation of Par-1 and the loss of cortical microtubules. Since non-phosphorylatable Par-1 is epistatic to uninhibitable Baz, Par-1 seems to function downstream of the other PAR proteins to polarise the oocyte microtubule cytoskeleton.