H2020Individual fellowship2016–2018

SAC_EarlyEmbryo · SAC robustness in the transition from meiosis to mitosis

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration: 2016-02-01 → 2018-01-31
EU contribution: €159,461
Participants: 1
Scheme: MSCA-IF-EF-ST

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Results in brief

SAC robustness in the transition from meiosis to mitosis

Maintenance of genomic integrity during meiosis and early embryogenesis is essential as chromosomal and genetic abnormalities transmitted through the gametes or blastomeres can result in pregnancy failures and/or severe fetal disorders. Although in somatic mitotic cells chromosome segregation is extremely trustworthy, different studies in mammals have shown that chromosome segregation errors are strikingly high in early embryonic development, estimating that between 22-80% of the pre-implantation embryos have cells with chromosomal abnormalities. This data suggests that the regulatory mechanisms that ensure faithful chromosome segregation that are very accurate in somatic cells, most importantly the spindle assembly checkpoint (SAC), may behave differently in the first divisions of the embryo. The SAC is a surveillance mechanism that monitors the presence of unattached chromosomes and inhibits anaphase onset until all the chromosomes are properly attached to microtubules. The relevance and dynamics of the SAC, safeguarding genome integrity, in dividing somatic cells have been deeply studied and it is well established that defects in this checkpoint leads to chromosome missegregation. However, despite the importance for early embryonic development, the sensitivity of mammalian embryos to light has precluded real-time imaging of chromosome segregation and its control in the first embryonic divisions. Recent advances in light sheet microscopy in the Ellenberg lab have now overcome this limitation. Taking advantage of this unique opportunity I have studied how chromosome segregation takes place during the first embryonic divisions.

Data: CORDIS, © European Union

Project objective

Meiotic divisions in the oocyte have been shown to be surprisingly error-prone compared to the reliable chromosome segregation that takes place in dividing somatic cells. The high frequency of chromosomal abnormalities found in pre-implantation embryos in mammals coupled with the fact that the first divisions of the embryo resembles meiosis in several aspects suggests that the mechanisms controlling chromosome segregation, most importantly the spindle assembly checkpoint (SAC), only become fully operational after the transition from meiosis to mitosis during early development. Despite the importance for early embryonic development, the sensitivity of mammalian embryos to light and the absence of a functional reporter of the SAC in mice have precluded real-time imaging of chromosome segregation and its control in the first embryonic divisions. Recent advances in light sheet microscopy in the Ellenberg lab now allow me to study chromosome segregation. In addition, in collaboration with the EMBL Transgenic Facility I will be able to rapidly generate the first SAC reporter mice that will permit me to test the checkpoint functionality up to the blastocyst stage.Taking advantage of this unique opportunity to combine new technology with a novel reporter animal model, I plan to study how the SAC changes from meiosis to the first embryonic divisions of blastocysts. To this end, I will analyze SAC signalling and dynamics and assess whether the robustness of the SAC increases with development. My project aims to improve our understanding of chromosome segregation during mammalian pre-implantation development, and therefore the results of my research will be important to shed light on the molecular causes of aneuploidy in the early embryo, fundamental for our understanding of infertility and to improve the process of in vitro fertilization.

Original text from CORDIS.

Participants

EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergCoordinatorGermany

SAC_EarlyEmbryo · SAC robustness in the transition from meiosis to mitosis

Results in brief

SAC robustness in the transition from meiosis to mitosis

Project objective

Participants

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