Irion Uwe, Leptin Maria, Siller Karsten, Fuerstenberg Sal, Cai Yu, Doe Chris Q, Chia William, Yang Xiaohang
Institut für Genetik, Universität zu Köln, Weyertal 121, D-50931, Cologne, Germany.
Curr Biol. 2004 Jan 20;14(2):138-44. doi: 10.1016/j.cub.2004.01.002.
Asymmetric cell division generates cell diversity in bacteria, yeast, and higher eukaryotes. In Drosophila, both neural and muscle progenitors divide asymmetrically. In these cells the Inscuteable (Insc) protein complex coordinates cell polarity and spindle orientation. Abstrakt (Abs) is a DEAD-box protein that regulates aspects of cell polarity in oocytes and embryos. We use a conditional allele of abs to investigate its role in neural and muscle progenitor cell polarity. In neuroblasts we observe loss of apical Insc crescents, failure in basal protein targeting, and defects in spindle orientation. In the GMC4-2a cell we observe loss of apical Insc crescents, defects in basal protein targeting, and equalization of sibling neuron fates; muscle precursors show a similar equalization of sibling cell fates. These phenotypes resemble those of insc mutants; indeed, abs mutants show a striking loss of Insc protein levels but no change of insc RNA levels. Furthermore, we find that the Abs protein physically interacts with insc RNA. Our results demonstrate a novel role for Abs in the posttranscriptional regulation of insc expression, which is essential for proper cell polarity, spindle orientation, and the establishment of distinct sibling cell fates within embryonic neural and muscle progenitors.
不对称细胞分裂在细菌、酵母和高等真核生物中产生细胞多样性。在果蝇中,神经祖细胞和肌肉祖细胞都会进行不对称分裂。在这些细胞中,无柄蛋白(Inscuteable,Insc)复合物协调细胞极性和纺锤体定向。抽象蛋白(Abstrakt,Abs)是一种DEAD盒蛋白,可调节卵母细胞和胚胎中细胞极性的多个方面。我们利用abs的一个条件等位基因来研究其在神经和肌肉祖细胞极性中的作用。在神经母细胞中,我们观察到顶端Insc月牙消失、基底蛋白靶向失败以及纺锤体定向缺陷。在GMC4-2a细胞中,我们观察到顶端Insc月牙消失、基底蛋白靶向缺陷以及姐妹神经元命运均等化;肌肉前体细胞也表现出类似的姐妹细胞命运均等化。这些表型与Insc突变体的表型相似;实际上,abs突变体中Insc蛋白水平显著降低,但insc RNA水平没有变化。此外,我们发现Abs蛋白与insc RNA存在物理相互作用。我们的结果证明了Abs在insc表达的转录后调控中具有新作用,这对于胚胎神经和肌肉祖细胞中正确的细胞极性、纺锤体定向以及不同姐妹细胞命运的建立至关重要。