Figure 5.

Aneuploidy in MCMBP-deficient parasites is likely caused by the formation of anaphase chromatin bridges and aberrant nuclear fission. Hypothetical model for the progression of mitosis and segmentation in MCMBP^HADD parasites either in the presence (left) or absence (right) of Shld1. In the presence of Shld1, nuclei with a single MTOC form a hemispindle. This hemispindle retracts and the MTOC duplicates and migrates to the opposing side of the nucleus to form the mitotic spindle. The two MTOCs then move away from each other, but remain connected by the interpolar spindle. The nucleus then undergoes nuclear fission in the DNA-free bridge region to form two daughter nuclei that each reform a hemispindle. The parasite undergoes multiple rounds of mitosis in this manner. MCMBP is no longer expressed when the parasite commits to segmentation and the formation of merozoites, where we observe subpellicular microtubules connecting the apical polar ring and basal complex. In the absence of Shld1, we observe aberrant hemispindles and mitotic spindles. After forming the mitotic spindle, these nuclei form interpolar spindles, but either form anaphase chromatin bridges and/or fail to undergo nuclear fission, which both lead to aneuploidy. Aneuploid nuclei continue to undergo further rounds of mitosis and do undergo segmentation. Segmentation, however, leads to the formation of cells of various sizes, including zoid parasites, which lack nuclei, and large merozoites that contain multiple sets of organelles and more than 1n DNA content. Blue = nuclei, purple = microtubules, greyscale = MTOC or rhoptries (in merozoites). n = number of genome copies, ?n = unknown/uneven genome content.