An ex vivo system to study cellular dynamics underlying mouse peri-implantation development

Area of Science:

• Developmental Biology
• Embryology
• Biophysics

Background:

• Mammalian embryonic development involves complex morphogenesis, including axis specification and gastrulation, which are difficult to study due to limited accessibility.
• Understanding peri-implantation development is crucial for deciphering early life stages and potential developmental disorders.

Purpose of the Study:

• To develop a novel ex vivo culture system for recapitulating mouse embryonic development from E4.5 to E6.0.
• To enable in toto monitoring and analysis of cellular dynamics during early mammalian development.
• To investigate the role of mechanical forces in embryonic morphogenesis and patterning.

Main Methods:

• Development of a Matrigel-collagen-based 3D ex vivo culture system for mouse embryos.
• Utilizing light-sheet microscopy for live imaging and automatic cell segmentation.
• Quantifying embryonic growth, axis initiation, and 3D architecture.

Main Results:

• The system successfully recapitulated mouse embryonic growth, axis initiation, and 3D architecture in 49% of cases.
• Observed that polar trophectoderm constriction and invagination are necessary for development, driven by tension release.
• Demonstrated the crucial role of extra-embryonic ectoderm in epiblast growth, morphogenesis, and patterning.

Conclusions:

• The developed 3D ex vivo system provides unprecedented access to peri-implantation development.
• Revealed a critical mechano-chemical interplay between extra-embryonic and embryonic tissues during early development.
• This system facilitates in toto monitoring, measurement, and perturbation for studying developmental processes.