Study on the asymmetric cell division of neural stem cells

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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.