Changing Mad2 levels affects chromosome segregation and spindle assembly checkpoint control in female mouse meiosis I.
The spindle assembly checkpoint (SAC) ensures correct separation of sister chromatids in somatic cells and provokes a cell cycle arrest in metaphase if one chromatid is not correctly attached to the bipolar spindle. Prolonged metaphase arrest due to overexpression of Mad2 has been shown to be deleterious to the ensuing anaphase, leading to the generation of aneuploidies and tumorigenesis. Additionally, some SAC components are essential for correct timing of prometaphase. In meiosis, we and others have shown previously that the Mad2-dependent SAC is functional during the first meiotic division in mouse oocytes. Expression of a dominant-negative form of Mad2 interferes with the SAC in metaphase I, and a knock-down approach using RNA interference accelerates anaphase onset in meiosis I. To prove unambigiously the importance of SAC control for mammalian female meiosis I we analyzed oocyte maturation in Mad2 heterozygote mice, and in oocytes overexpressing a GFP-tagged version of Mad2. In this study we show for the first time that loss of one Mad2 allele, as well as overexpression of Mad2 lead to chromosome missegregation events in meiosis I, and therefore the generation of aneuploid metaphase II oocytes. Furthermore, SAC control is impaired in mad2+/- oocytes, also leading to the generation of aneuploidies in meiosis I.
Niault
Théodora
T
CNRS UMR7622 Biologie du Développement, Paris, France.
Hached
Khaled
K
Sotillo
Rocío
R
Sorger
Peter K
PK
Maro
Bernard
B
Benezra
Robert
R
Wassmann
Katja
K
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002875:Chromosomes; D005260:Female; D064246:Mad2 Proteins; D008540:Meiosis; D051379:Mice; D008941:Spindle Apparatus
D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse