Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis

Marion Manil-Ségalen (1) , Małgorzata Łuksza (1) , Joanne Kanaan (1) , Véronique Marthiens (2) , Simon I R Lane (3) , Keith T Jones (3) , Marie-Emilie Terret (1) , Renata Basto (2) , Marie-Hélène Verlhac (1)

1 CIRB - Centre interdisciplinaire de recherche en biologie
2 Biologie Cellulaire et Cancer
3 University of Southampton

Rockefeller University Press 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.

Domaines: Sciences du Vivant [q-bio]

Marion Manil-Ségalen, Małgorzata Łuksza, Joanne Kanaan, Véronique Marthiens, Simon I R Lane, et al.. Chromosome structural anomalies due to aberrant spindle forces exerted at gene editing sites in meiosis. Journal of Cell Biology, 2018, 217, pp.3416 - 3430. ⟨10.1083/jcb.201806072⟩. ⟨hal-03455108⟩