Turning point in a lifetime

A new microscope can record the first days of a mouse embryo from fertilization until implantation in it's mother's womb.

For the first time, scientists observed the first two to three days of a mouse embryo's life, as it developed from a fertilised egg to when it implanted in the uterus. All thanks to a new light sheet microscope developed at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany.

"When I first saw the videos, I said 'This is a breakthrough - nobody has ever seen this before!' The beginning of our own lives looks like this, and we could never look at it before. Now there's so much we can learn!"

Jan Ellenberg PhD, Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany and corresponding author.

Starting from the first cell and its very first division, EMBL scientists tracked each daughter cell to that original cell, then each grand-daughter, great-granddaughter and so on. At any given moment, they knew each cell's exact family tree. This has enabled them to identify a crucial turning point in the embryo's life.

When the embryo is still a sphere of 8 cells, about the human equivalent of Carnegie Stages 2 to 3, the direction of division stops being random.

In that single moment, instead of all cells moving outward in the same direction — one of the daughter cells forms towards the inside of the sphere of cells.

From this point on, the fate of a cell's lineage is set. Cells on the inside will continue on to become the embryo. Those on the outside will become part of the placenta that supports and nurtures the embryo in the uterus.

The findings and technology enabling them, are published in Nature Methods.

"People have been really excited whenever I've presented this technology and our results with it," says Ellenberg, "and not just people doing fundamental research; people working in fertility clinics are really interested, too."

About the work:
Despite its importance for understanding human infertility and congenital diseases, early mammalian development has remained inaccessible to in toto imaging. We developed an inverted light-sheet microscope that enabled us to image mouse embryos from zygote to blastocyst, computationally track all cells and reconstruct a complete lineage tree of mouse pre-implantation development. We used this unique data set to show that the first cell fate specification occurs at the 16-cell stage.

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Scientists can now view and track the first days of a mouse embryo's life
and watch as embryonic cells begin to move into position. Outside cells
to become support structures while inside cells become the embryo itself .

Image Credit: EMBL/Julius Hossain