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New microscope offers 4-D look at embryonic development in living mice

For the first time, researchers can now peek inside a living mouse embryo and watch the gut begin to form and heart cells take their first tentative beats. Over a critical 48-hour window—when rudimentary organs begin to take shape—scientists can follow every embryonic cell and pinpoint where it went, what genes it turned on, and what cells it met along the way.

The new work is "literally a cellular-resolution building plan of the entire mouse," says Philipp Keller, a physicist and biologist at the Howard Hughes Medical Institute's Janelia Research Campus in Ashburn, Virginia. He and his colleagues report the results October 11, 2018, in the journal Cell. And they're making the microscope and computational tools, built at Janelia, and all the imaging data free and publicly available.

Such resources are critical for scientists trying to grow or regenerate organs, or to one day fix developmental problems that arise in the womb, says Kate McDole, a Janelia developmental biologist and study coauthor. "To do any of that, you first need to understand how organs form," she says. "You need to actually see what happens in a real embryo."

[...] At the center of the Janelia researchers' microscope, a clear, acrylic cube houses the embryo imaging chamber. Two light sheets illuminate the embryo, and two cameras record images. Those components let researchers spy the once-unseen world of early organ development, revealing dynamic events in high-resolution detail no one has seen before.

[...] The microscope's brain is equipped with a suite of algorithms that track the embryo's position and size. These algorithms map how the light sheet moves through the sample and then figure out how to get the best-looking images—keeping the embryo focused and centered in the field of view.

Because the embryo is constantly changing, the microscope must constantly adapt, making decisions in milliseconds, over hundreds of images, at hundreds of different time points. "I wouldn't say our microscope is smarter than a human," Keller says, "but it's capable of doing things that a human operator would not be able to do."

In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level (DOI: 10.1016/j.cell.2018.09.031)

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