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Compaction mechanisms in the early embryo

The early events during embryo development are central for subsequent cell specification. European researchers investigated the mechanism of cell positioning and identified an intriguing role for cell contractility.
Compaction mechanisms in the early embryo
During early development, the blastocyst consists of an epithelial layer encapsulating the inner-cell mass (ICM) that gives rise to all embryonic tissues. The positioning of blastomeres at the surface or inside the embryo determines their subsequent differentiation into trophectoderm or ICM, respectively. Cell-to-cell contacts promote the expression of pluripotency genes, while the apical membrane promotes trophectoderm genes through a mechanism that is not completely understood.

After division to the 16-cell stage, only blastomeres destined to form the ICM would show prominent periodic contractions. This divergent behaviour between sister cells suggests an asymmetry in the division of components of the contractile apparatus.

To further investigate this, scientists of the MECHACOMPA (Mechanics of compaction in the mouse pre-implantation embryo) project studied the functional relationship between apical proteins and contractility.

Close inspection of the apical domain revealed its low levels in actin and myosin, indicating that it constitutes a domain of low contractility. When inherited by one daughter cell only, it generates heterogeneities in the contractility of sister blastomeres and could explain their different positioning within the embryo.

To examine whether differences in contractility are responsible for the positioning of the precursors to the ICM, MECHACOMPA mixed blastomeres that were engineered to have different contractility. They observed that contractility was sufficient to control the positioning of cells within the pre-implantation embryo.

Mechanistic insight was provided through a three-dimensional model of the 16-cell stage that had cells with different contractility. This model successfully recapitulated the shapes and movements observed in experiments and further predicted that internalisation occurred whenever the tension of a blastomere exceeded that of its neighbouring counterparts by 1.5 times. This quantitative prediction was then confirmed and tested experimentally.

Intriguingly, disturbances in contractility affected not only internalisation but fate specification as well, and caused cells to adopt an embryonic tissue fate. Researchers speculated that the association between contractility, positioning and fate specification of the blastomeres may be due to some type of mechanosensing.

Collectively, MECHACOMPA findings provide unprecedented evidence on the mechanisms controlling fate specification in the mammalian embryo. This brings us a step closer to unravelling the complex initial steps in embryo development.

Related information

Keywords

Embryo, inner cell mass, blastomere, MECHACOMPA, contractility
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