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. Author manuscript; available in PMC: 2020 Aug 22.
Published in final edited form as: Cell. 2019 Aug 8;178(5):1132–1144.e10. doi: 10.1016/j.cell.2019.07.001

Figure 1. Biased flipping underlies the biased orientation of selfish centromeres towards the egg pole.

Figure 1.

(A) Schematic of female meiosis. The meiosis I (MI) spindle initially forms in the center of the oocyte and later migrates towards the cortex and orients perpendicular to the cortex, followed by the highly asymmetric cell division. Selfish elements cheat by preferentially orienting to the egg side of the spindle. (B) Schematic of the intraspecific CHPO hybrid system for centromere drive. A Mus musculus strain with larger (L) centromeres, CF-1, is crossed to a strain with smaller (S) centromeres, CHPO. In the hybrid offspring, chromosomes with larger and smaller centromeres are paired in meiotic bivalents. (C) Schematic showing spindle asymmetry and biased orientation of larger centromeres in the intraspecific CHPO hybrid, based on previous results (Akera et al., 2017). Initial MT attachments are established when the spindle is still in the center and symmetric. Hybrid bivalents are off-center on the spindle, with the larger centromere closer to the pole, indicating that larger and smaller centromeres interact differentially with spindle MTs. Bivalent orientation on the spindle is unbiased right after spindle migration (early meta I), but the attachment of larger centromeres to the cortical side of the spindle is especially unstable, leading to detachment and flipping to establish biased orientation (late meta I). (D) CF-1 x CHPO (L x S) hybrid oocytes expressing CENP-B-mCherry and H2B-EGFP were imaged live after spindle migration. Time-lapse images show examples of flipping events to face larger centromeres towards the egg (top) or cortical (bottom, 0 – 30 min) side. Images are maximum intensity z-projections showing all chromosomes (left), or optical slices magnified to show flipping events (timelapse). Orange and white arrows indicate larger and smaller centromeres, respectively. Scale bar, 10 μm. Percentages indicate the frequency of each case (n = 21 flipping events from 48 cells). *P < 0.05, indicating significant deviation from 50%. Two out of four flipping events that faced larger centromeres towards the cortical side were subsequently reversed (bottom, 30 – 60 min), demonstrating the difficulty for larger centromeres to remain attached to the cortical side.