The Drosophila NuMA Homolog Mud Regulates Spindle Orientation in Asymmetric Cell Division

During asymmetric cell division, the mitotic spindle must be properly oriented to ensure the asymmetric segregation of cell fate determinants into only one of the two daughter cells. In Drosophila neuroblasts, spindle orientation requires heterotrimeric G proteins and the Gα binding partner Pins, but how the Pins-Gαi complex interacts with the mitotic spindle is unclear. Here, we show that Pins binds directly to the microtubule binding protein Mud, the Drosophila homolog of NuMA. Like NuMA, Mud can bind to microtubules and enhance microtubule polymerization. In the absence of Mud, mitotic spindles in Drosophila neuroblasts fail to align with the polarity axis. This can lead to symmetric segregation of the cell fate determinants Brat and Prospero, resulting in the misspecification of daughter cell fates and tumor-like overproliferation in the Drosophila nervous system. Our data suggest a model in which asymmetrically localized Pins-Gαi complexes regulate spindle orientation by directly binding to Mud.