Study on the asymmetric cell division of neural stem cells

果蝇神经母细胞为研究不对称细胞分裂和潜在的细胞极性提供了一个极好的平台。这些细胞经历典型的不对称分裂，在此过程中，细胞命运决定因素定位于基底皮质，有丝分裂纺锤体沿顶基轴定向，大小不等的子细胞出现。在这项研究中，我们进行了大规模的基因筛选，以确定在神经母细胞不对称分裂突变缺陷。在我们在本研究中发现的突变中，新基因座的突变分类如下：1)两个突变（4个等位基因）破坏子细胞之间的细胞大小不对称，但不影响miranda等决定因素的不对称定位。2)三个突变（5个等位基因）使有丝分裂纺锤体取向与细胞轴分离，但不影响成神经细胞的细胞极性。3)一个突变体在细胞极性相对于下层上皮的正确方向上有缺陷。两个突变导致细胞命运决定因子的异常分布。1类基因座分别编码异三聚体G蛋白的Gβ 13f亚基和Gyl亚基，形成皮质复合体，表明G蛋白信号参与决定子细胞大小的比例。我们还发现，第2类位点编码蘑菇体缺陷（mud）基因，该基因是从成人脑组织缺陷突变体中鉴定出来的。这一发现为阐明有丝分裂纺锤体取向与细胞极性耦合的机制提供了线索。

Drosophila neuroblasts provide an excellent platform to study asymmetric cell division and underlying cell polarity. Those cells undergo typical asymmetric divisions, during which cell-fate determinants localize to the basal cortex, mitotic spindles orient along the apical-basal axis, and unequal-sized daughter cells appear. In this study, we have carried out a large scale genetic screen to identify mutants defective in the neuroblasts asymmetric division. Among mutations that we identified in this study, mutations for new loci are classified as follows ;1) Two mutations (4 alleles) disrupt cell size asymmetry between the daughters but not asymmetric localization of the determinants such as Miranda.2) Three mutations (5 alleles) uncouple mitotic spindle orientation from the cell axis without affecting the cell polarity of neuroblasts.3) One mutant is defective in correct orientation of the cell polarity relative to the underlying epithelia.4) Two mutations cause an abnormal distribution of the cell fate determinants.The class 1 loci turned out to be genes encoding Gβ13F and Gyl subunits of heterotrimeric G proteins, respectively, which form a cortical complex, revealing that G protein signaling is involved in determining the ration in daughter cell size. We also revealed that the class 2 locus encodes the mushroom body defect (mud) gene, which had been identified from mutants defective in the adult brain organization. This finding provides a clue to elucidate a mechanism by which mitotic spindle orientation is coupled to cell polarity.