Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells

Abstract

During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs.

Planar Pol(o)arity

“…Together with other recent studies of apicobasal polarity (Bell et al, 2015;Besson et al, 2015;Carvalho et al, 2015), the new work on planar polarity gives us a frontrow seat from which to view the action.…”

Tissue morphodynamics: Translating planar polarity cues into polarized cell behaviors

“…Symmetry breaking in SOPs occurs during interphase, at least two hours prior to mitosis, as PAR complex proteins (Par3/Bazooka, aPKC, and Par6) become enriched on the Fz side of the cortex [63]. The posterior enrichment of the PAR complex leads to the phosphorylation of Numb by aPKC and its exclusion from the posterior, and thus, its restriction to the anterior side [62].…”

“…The posterior enrichment of the PAR complex leads to the phosphorylation of Numb by aPKC and its exclusion from the posterior, and thus, its restriction to the anterior side [62]. The initial bias of PAR proteins relies on PCP function, as Fz, Vang , and Dsh mutants show no bias in interphase PAR protein enrichment [63]. Later in mitosis, however, PAR proteins still polarize even in the absence of PCP, but their asymmetry is randomized with respect the anterior-posterior axis [64, 65].…”

“…Later in mitosis, however, PAR proteins still polarize even in the absence of PCP, but their asymmetry is randomized with respect the anterior-posterior axis [64, 65]. Thus, PCP breaks the initial symmetry of SOPs cells, but a mitotic rescue mechanism restores PAR (and thus, Numb) polarity [63]. How PCP proteins cause a shift in the localization of apical PAR complexes towards the posterior in SOP cells, but not in the surrounding epithelium, is not known.…”

Meru couples planar cell polarity with apical-basal polarity during asymmetric cell division

“…In most epithelial cells, these proteins localize uniformly around the cell cortex, whereas in SOPs they show a striking asymmetric localization during mitosis: the Baz-aPKC-Par6 complex is found at the posterior cell cortex, opposite an anterior complex consisting of Dlg, Partner of Inscuteable (Pins) and the G-protein subunit Gα i (Schaefer et al, 2001; Bellaïche et al, 2001b). The Fz-Dsh complex provides the spatial information for the Baz-aPKC-Par6 complex, while Vang-Pk positions the Dlg-Pins-Gα i complex (likely through direct interaction between Vang and Dlg) (Bellaïche et al, 2004; Besson et al, 2015; Bellaïche et al, 2001b). The asymmetric distribution of the polarity determinants then directs the positioning of cell fate determinants at the anterior cell cortex (Bellaïche et al, 2004, 2001a, 2001b; Wirtz-Peitz et al, 2008).…”