Non-apical mitoses contribute to cell delamination during mouse gastrulation

Area of Science:

• Developmental biology
• Cell biology
• Computational modeling

Background:

• Epithelial-mesenchymal transition (EMT) is crucial for gastrulation.
• Non-apical cell divisions occur at the primitive streak during mouse gastrulation.
• Non-apical mitoses may contribute to cell delamination from the epiblast.

Purpose of the Study:

• Investigate molecular determinants of mitosis position in the epiblast.
• Understand the role of non-apical mitoses in cell delamination.
• Analyze factors influencing cell division orientation during gastrulation.

Main Methods:

• Computational modeling of epiblast development.
• Pharmacological treatments of mouse embryos.
• Experiments using stem cell-based epiblast spheroids.

Main Results:

• Blocking basement membrane degradation did not affect mitosis asymmetry.
• Disrupting the actomyosin cytoskeleton or cell cycle dynamics induced ectopic non-apical mitosis.
• The primitive streak exhibits local actomyosin relaxation and less stringent cell cycle regulation.

Conclusions:

• Actomyosin cytoskeleton relaxation and cell cycle regulation are key determinants of non-apical mitosis.
• These factors are essential for normal primitive streak dynamics.
• Non-apical mitosis at the streak promotes cell delamination from the epiblast.