Differential functions of G protein and Baz–aPKC signaling pathways in Drosophila neuroblast asymmetric division

Abstract

Drosophila melanogaster neuroblasts (NBs) undergo asymmetric divisions during which cell-fate determinants localize asymmetrically, mitotic spindles orient along the apical–basal axis, and unequal-sized daughter cells appear. We identified here the first Drosophila mutant in the Gγ1 subunit of heterotrimeric G protein, which produces Gγ1 lacking its membrane anchor site and exhibits phenotypes identical to those of Gβ13F, including abnormal spindle asymmetry and spindle orientation in NB divisions. This mutant fails to bind Gβ13F to the membrane, indicating an essential role of cortical Gγ1–Gβ13F signaling in asymmetric divisions. In Gγ1 and Gβ13F mutant NBs, Pins–Gαi, which normally localize in the apical cortex, no longer distribute asymmetrically. However, the other apical components, Bazooka–atypical PKC–Par6–Inscuteable, still remain polarized and responsible for asymmetric Miranda localization, suggesting their dominant role in localizing cell-fate determinants. Further analysis of Gβγ and other mutants indicates a predominant role of Partner of Inscuteable–Gαi in spindle orientation. We thus suggest that the two apical signaling pathways have overlapping but different roles in asymmetric NB division.

Insights into neural stem cell biology from flies

“…This suggests that the Par and the Pins/Gai complexes function through different pathways (Parmentier et al 2000;Cai et al 2003). The heterotrimeric G protein subunits Gb13F and Gg1, both of which are distributed uniformly at the cortex, have also been shown to participate in the generation of unequalsized neuroblast daughters (Fuse et al 2003;Izumi et al 2004). The current model suggests that Pins and Loco act upstream of Gbg, but that Gbg signalling is also necessary to maintain Pins/Gai and Loco/Gai complexes at the apical cortex of neuroblasts, which would indicate that there is a feedback loop (reviewed by Bellaiche & Gotta 2005).…”

Polarity Control of Spindle Positioning in the C. elegans Embryo

“…5.4). Similarly, Drosophila Pins associates with Gαi and the LIN-5/NuMA-related protein Mud in NBs and epithelial cells (Izumi et al 2004;Bowman et al 2006;Siller and Doe 2009). Moreover, mammalian LGN recruits the NuMA protein to the cell cortex and simultaneously interacts with Gαi (Du and Macara 2004).…”

Analysis of neural stem cell self-renewal and differentiation by transgenic RNAi in Drosophila

“…The Pins, Gαi, Loco, and Mud proteins are linked to the Par complex through Insc and are required for spindle orientation [37][38][39][40][41][42][43][44][45]. Although all three proteins of the Par complex are preferentially segregated into the new neuroblast after cell division, and mutations in any of them affect the localization of the other apical proteins and the spindle orientation, the Par complex does not seem to control cell fate directly [8].…”