Abstract
Mouse female meiotic spindles assemble from acentriolar microtubule-organizing centers (aMTOCs) that fragment into discrete foci. These are further sorted and clustered to form spindle poles, thus providing balanced forces for faithful chromosome segregation. To assess the impact of aMTOC biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master microtubule-organizing center regulator. Excessive microtubule nucleation from these fragmented aMTOCs accelerated spindle assembly dynamics. Prematurely formed spindles promoted the breakage of three different fragilized bivalents, generated by the presence of recombined Lox P sites. Reducing the density of microtubules significantly diminished the extent of chromosome breakage. Thus, improper spindle forces can lead to widely described yet unexplained chromosomal structural anomalies with disruptive consequences on the ability of the gamete to transmit an uncorrupted genome.
Highlights
The microtubule (MT) spindle enables equal segregation of chromosomes between daughter cells during mitosis and meiosis
By co-staining with the pericentriolar material (PCM) component, Pericentrin (Fig. 1A top left panel), we showed that Plk4 localizes to acentriolar MTOCs (aMTOCs) arguing that it is not a limiting factor for centriole assembly in oocytes
Fragmentation of aMTOCs at nuclear envelope breakdown (NEBD) is normally concomitant with a burst in local MT assembly around chromosomes (Dumont et al, 2007; Schuh and Ellenberg, 2007)
Summary
The microtubule (MT) spindle enables equal segregation of chromosomes between daughter cells during mitosis and meiosis. In which one kinetochore of a chromosome is attached to both spindle poles, are common in tumour cells with extra-centrosomes (Ganem et al, 2009). These attachment errors cause chromosome mis-segregation at mitotic exit (Cimini et al, 2001), and subsequent formation of micronuclei and chromothripsis in daughter cells (Cimini et al, 2001; Crasta et al, 2012; Zhang et al, 2015)
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