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When the video above begins, this blue spot that moves, seen under a new high-resolution microscope, does not look like much anymore. But in just 26 seconds, you and I can see the tiny blob cells multiply, interact and organize in the first organic systems of a living mouse embryo.
The hollow crater forming on the left will give rise to the stomach, pancreas and liver of the mouse. The narrow white line that extends to the center of the image is the notochord or early spine. And the contracting region on the far left of the image marks the beginning of a heartbeat.
Researchers at the Janelia Research Institute campus of the Howard Hughes Medical Institute in Ashburn, Virginia, buiIt is a new microscope capable of tracing the origins and movements of individual cells in real time, thus drawing a virtual map of the evolution of mammalian development in the womb.
"We were previously limited to snapshots, like reading random pages from a book," said Kate McDole, developmental biologist and co-author of the study. "But how are the organs really formed? What is the timing, the tissues, the dynamics involved? You can only study this by watching it live.
"This work fills all gaps and tells a complete story," added Dr. McDole.
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The research team, led by Philipp Keller, a physicist and biologist, has striven to overcome the limitations of confocal microscopy, a traditional imaging method that illuminates an entire sample for long periods.
This method was too hard for the delicate embryonic cells of a mouse. "You would do it in the microwave," said Dr. McDole.
The new microscope – a transparent acrylic cube with a central chamber – has two cameras and two plates of light of a finesse of a razor illuminating only small parts of the specimen when it is absorbed by a rich fluid in nutrients. Every few milliseconds, the algorithms allow for the changing position of the embryo, the angle at which the bright leaves strike it and the best direction to capture a clear image.
The team collected nearly one million images of each live embryo and compiled them, said Dr. Keller.
With the help of a cell tracking program, they followed each individual cell for a critical 48-hour period – from six and a half days to eight and a half days after fertilization – during which time they were treated. embryo had reached a sesame seed and its vital organs begin to form.
Below, embryonic stem the cells fold to form the heart of a mouse. Each white point is an individual cell, migrating to create an atrium, the endocardial membrane (the emerging "X" shape) and finally a heartbeat.
The team also created a cell division detector to track when, where and which cells divide, as well as a toolhat represents a virtual "middle" mouse embryo by aligning four of the samples. (They called it TARDIS after the vehicle that carries the doctor and his companions in time and space. on "Doctor Who.")
Scientists are not allowed to experiment with human embryos. But by visualizing how organs form in mice, this research could help doctors study developmental problems inside the belly of humans.
A congenital abnormality called spina bifida, for example, occurs when part of the neural tube of the fetus does not close properly. The sequence below – captured from below, with the head to the left and the tail to the right – shows the neural tube closing as it should.
Watch as the two lines forward that extend across the embryo come together, with somites (later, ribs) forming on each side.
Researchers also believe that in the long term, the study of moving plans could inform scientists' efforts to grow or regenerate organs in a laboratory.
"Put a pile of stem cells in a dish, pour chemicals and create objects that look like heart cells. But that only gives you the basics, "said Dr. McDole. "You can not take the pieces of a house and throw them in piles. What we are doing here is really trying to understand how the roof works. "
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