Lethal giant larvae controls the localization of notch-signaling regulators numb, neuralized, and Sanpodo in Drosophila sensory-organ precursor cells

Asymmetric distribution of fate determinants is a fundamental mechanism underlying the acquisition of distinct cell fates during asymmetric division. In Drosophila neuroblasts, the apical DmPar6/DaPKC complex inhibits Lethal giant larvae (Lgl) to promote the basal localization of fate determinants [1-3]. In contrast, in the sensory precursor (pl) cells that divide asymmetrically with a planar polarity, Lgl inhibits Notch signaling in the anterior pl daughter cell, pIIb, by a yet-unknown mechanism [4]. We show here that LgI promotes the cortical recruitment of Partner of Numb (Pon) and regulates the asymmetric distribution of the fate determinants Numb and Neuralized during the pi cell division. Analysis of Pon-GFP and Histone2B-mRFP distribution in two-color movies confirmed that LgI regulates Pon localization. Moreover, posterior DaPKC restricts LgI function to the anterior cortex at mitosis. Thus, LgI functions similarly in neuroblasts and in pl cells. We also show that LgI promotes the acquisition of the pIIb cell fate by inhibiting the plasma membrane localization of Sanpodo and thereby preventing the activation of Notch signaling in the anterior pi daughter cell. Thus, LgI regulates cell fate by controlling Pon cortical localization, asymmetric localization of Numb and Neuralized, and plasma-membrane localization of Sandopo.