PDF(Pubmed)
Abstract：
Asymmetric cell division is an important mechanism that generates cellular diversity during development. Not only do asymmetric cell divisions produce daughter cells of different fates, but many can also produce daughters of different sizes, which we refer to as Daughter Cell Size Asymmetry (DCSA). In Caenorhabditis elegans, apoptotic cells are frequently produced by asymmetric divisions that exhibit DCSA, where the smaller daughter dies. We focus here on the divisions of the Q.a and Q.p neuroblasts, which produce larger surviving cells and smaller apoptotic cells and divide with opposite polarity using both distinct and overlapping mechanisms. Several proteins regulate DCSA in these divisions. Previous studies showed that the PIG-1/MELK and TOE-2 proteins regulate DCSA in both the Q.a and Q.p divisions, and the non-muscle myosin NMY-2 regulates DCSA in the Q.a division but not the Q.p division. In this study, we examined endogenously tagged NMY-2, TOE-2, and PIG-1 reporters and characterized their distribution at the cortex during the Q.a and Q.p divisions. In both divisions, TOE-2 localized toward the side of the dividing cell that produced the smaller daughter, whereas PIG-1 localized toward the side that produced the larger daughter. As previously reported, NMY-2 localized to the side of Q.a that produced the smaller daughter and did not localize asymmetrically in Q.p. We used temperature-sensitive nmy-2 mutants to determine the role of nmy-2 in these divisions and were surprised to find that these mutants only displayed DCSA defects in the Q.p division. We generated double mutant combinations between the nmy-2 mutations and mutations in toe-2 and pig-1. Because previous studies indicate that DCSA defects result in the transformation of cells fated to die into their sister cells, the finding that the nmy-2 mutations did not significantly alter the Q.a and Q.p DCSA defects of toe-2 and pig-1 mutants but did alter the number of daughter cells produced by Q.a and Q.p suggests that nmy-2 plays a role in specifying the fates of the Q.a and Q.p that is independent of its role in DCSA.
摘要：
不对称细胞分裂是在发育过程中产生细胞多样性的重要机制。不对称细胞分裂不仅产生不同命运的子细胞，但是许多人也可以生产不同大小的女儿，我们称之为子细胞大小不对称(DCSA)。在秀丽隐杆线虫中,凋亡细胞通常由表现出DCSA的不对称分裂产生，小女儿死的地方.我们在这里关注Q.a和Q.p神经母细胞的划分，它们产生更大的存活细胞和更小的凋亡细胞，并使用不同和重叠的机制以相反的极性分裂。几种蛋白质在这些分裂中调节DCSA。先前的研究表明，PIG-1/MELK和TOE-2蛋白在Q.a和Q.p部门中调节DCSA，非肌肉肌球蛋白NMY-2调节Q.a分区的DCSA，但不调节Q.p分区。在这项研究中,我们检测了内源性标记的NMY-2,TOE-2和PIG-1报告基因,并对它们在Q.a和Q.p分裂过程中在皮质的分布进行了表征.在这两个部门中，TOE-2位于产生较小女儿的分裂细胞一侧，而PIG-1位于产生较大女儿的一侧。正如以前报道的那样，NMY-2位于产生较小女儿的Q.a的一侧，并且在Q.p中没有不对称地定位。我们使用温度敏感的nmy-2突变体来确定nmy-2在这些分区中的作用，并惊讶地发现这些突变体仅在Q.p分区中显示DCSA缺陷。我们在nmy-2突变与toe-2和pig-1突变之间产生了双突变组合。因为以前的研究表明DCSA缺陷会导致注定死亡的细胞转化为姐妹细胞，发现nmy-2突变并未显着改变toe-2和pig-1突变体的Q.a和Q.pDCSA缺陷，但确实改变了Q.a和Q.p产生的子细胞数量，这表明nmy-2在确定Q.a和Q.p的命运中起着独立于其在DCSA中的作用的作用。
