Summary
Early animal embryos undergo a profound reprogramming of cell behaviour at the blastula stage in a major developmental transition known as the mid-blastula transition (MBT). Earlier studies demonstrated that MBT is an essential transition for embryonic development across various species, involving simultaneous changes in key cellular activities: activation of zygotic genome transcription (ZGA), cell cycle elongation, loss of division synchrony, and onset of cell motility. In contrast, little is known for mammalian embryos, which are often viewed as not having an MBT because of their slow initial cell cycle and early ZGA. However, MBT also exhibits a switch in the cell growth mode from reductive cleavage divisions to proliferative growth, and our recent findings suggest that this switch occurs at the blastocyst stage in mouse embryos. This project aims to identify the mammalian MBT, define its fundamental features and investigate the mechanisms that control its timing. Employing light-sheet microscopy to image mouse embryos at high spatiotemporal resolution, automatic cell segmentation and single-cell tracking, I will quantitatively characterise the cell volume dynamics in early embryogenesis. This will allow me to identify the transition from cleavage to proliferative growth and use this time reference to characterise novel MBT features. Specifically, I will focus on 18 hours within the blastocysts stage to test the hypothesis that mammalian MBT entails changes in cell fate, metabolism, spindle assembly and/or cell cycle control. Through temporally controlled perturbations I will determine if there is a causal link between these changes and identify the upstream regulator, the trigger for the mammalian MBT, as well as the mechanism by which the MBT timing is controlled. The identification and characterisation of mammalian MBT may provide a new definition and mechanism regulating this key transition in animal development.
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| Web resources: | https://cordis.europa.eu/project/id/101152220 |
| Start date: | 01-07-2025 |
| End date: | 30-06-2027 |
| Total budget - Public funding: | - 187 624,00 Euro |
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Original description
Early animal embryos undergo a profound reprogramming of cell behaviour at the blastula stage in a major developmental transition known as the mid-blastula transition (MBT). Earlier studies demonstrated that MBT is an essential transition for embryonic development across various species, involving simultaneous changes in key cellular activities: activation of zygotic genome transcription (ZGA), cell cycle elongation, loss of division synchrony, and onset of cell motility. In contrast, little is known for mammalian embryos, which are often viewed as not having an MBT because of their slow initial cell cycle and early ZGA. However, MBT also exhibits a switch in the cell growth mode from reductive cleavage divisions to proliferative growth, and our recent findings suggest that this switch occurs at the blastocyst stage in mouse embryos. This project aims to identify the mammalian MBT, define its fundamental features and investigate the mechanisms that control its timing. Employing light-sheet microscopy to image mouse embryos at high spatiotemporal resolution, automatic cell segmentation and single-cell tracking, I will quantitatively characterise the cell volume dynamics in early embryogenesis. This will allow me to identify the transition from cleavage to proliferative growth and use this time reference to characterise novel MBT features. Specifically, I will focus on 18 hours within the blastocysts stage to test the hypothesis that mammalian MBT entails changes in cell fate, metabolism, spindle assembly and/or cell cycle control. Through temporally controlled perturbations I will determine if there is a causal link between these changes and identify the upstream regulator, the trigger for the mammalian MBT, as well as the mechanism by which the MBT timing is controlled. The identification and characterisation of mammalian MBT may provide a new definition and mechanism regulating this key transition in animal development.Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
03-10-2024
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