Asymmetric cell division : mechanisms creating cell diversity from cell asymmetry

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Drosophila neuroblasts 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. We have carried out a large scale genetic screen to identify mutants defective in the neuroblasts asymmetric division.1.Among several mutants showing novel phenotypes, two mutations disrupt cell size asymmetry between the daughters but not asymmetric localization of the determinants such as Miranda. These genes encode G□13F and G□1 subunits of heterotrimeric G proteins, respectively, which form a cortical complex. In the wild type neuroblasts, the basal spindle half is smaller than the apical one, forming the smaller basal daughter. In contrast, elimination of G□□ results in a large symmetric spindle in random orientations and causes division into nearly equal-sized cell, suggesting a critical role of G□□in asymmetric spindle organization in neuroblasts.2.We also asked … More how spindle orientation is regulated by examining dividing epithelial cells and neuroblasts in those mutants ; it has been unclear because spindle orientation in neuroblasts is randomized by depleting any one of those components. It turned out that the spindle always points toward Pins location when it localizes asymmetrically, suggesting that Pines predominantly regulates spindle orientation. We are currently searching molecules acting with Pins to orient the mitotic spindle. By both genetic and biochemical screens, we identified Drosophila Mushroom body defect (Mud) as an essential factor in receptor-independent G protein signalling (Gαi and Pins) responsible for regulating spindle orientation in both cell types. Based on our study, we propose that Drosophila Mud, vertebrate NuMA and C.elegans Lin-5 play comparable roles in receptor-independent G-protein signalling and that these molecules, together with Pins GoLoco proteins and Gαi, constitute an essential part of a general mechanism regulating the mitotic spindle through interaction with astral microtubules. Less