Snapshots of Life: Muscling in on Development

Limb Muscles

Credit: Mary P. Colasanto, University of Utah, Salt Lake City

Twice a week, I do an hour of weight training to maintain muscle strength and tone. Millions of Americans do the same, and there’s always a lot of attention paid to those upper arm muscles—the biceps and triceps. Less appreciated is another arm muscle that pumps right along during workouts: the brachialis. This muscle—located under the biceps—helps your elbow flex when you are doing all kinds of things, whether curling a 50-pound barbell or just grabbing a bag of groceries or your luggage out of the car.

Now, scientific studies of the triceps and brachialis are providing important clues about how the body’s 40 different types of limb muscles assume their distinct identities during development [1]. In these images from the NIH-supported lab of Gabrielle Kardon at the University of Utah, Salt Lake City, you see the developing forelimb of a healthy mouse strain (top) compared to that of a mutant mouse strain with a stiff, abnormal gait (bottom).

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Snapshots of Life: Picturing the Developing Windpipe

Mouse trachea

Randee Young and Xin Sun, University of Wisconsin–Madison

The image above shows a small section of the trachea, or windpipe, of a developing mouse. Although it’s only about the diameter of a pinhead at this stage of development, the mouse trachea has a lot in common structurally with the much wider and longer human trachea. Both develop from a precisely engineered balance between the flexibility of smooth muscle and the supportive strength and durability of cartilage.

Here you can catch a glimpse of this balance. C-rings of cartilage (red) wrap around the back of the trachea, providing the support needed to keep its tube open during breathing. Attached to the ends of the rings are dark shadowy bands of smooth muscles, which are connected to a web of nerves (green). The tension supplied by the muscle cells is essential for proper development of those neatly organized cartilage rings.

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Snapshots of Life: Coming Face to Face with Development

Zebrafish larva

Credit: Oscar Ruiz and George Eisenhoffer, University of Texas MD Anderson Cancer Center, Houston

Zebrafish (Danio rerio) is a favorite model for studying development, in part because its transparent embryos make it possible to produce an ever-growing array of amazingly informative images. For one recent example, check out this Federation of American Societies for Experimental Biology’s 2016 BioArt winner, which shows the developing face of a 6-day-old zebrafish larva.

Yes, those downturned “lips” are indeed cells that will go on to become the fish’s mouth. But all is not quite what it appears: the two dark circles that look like eyes are actually developing nostrils. Both the nostrils and mouth express high levels of F-actin (green), a structural protein that helps orchestrate cell movement. Meanwhile, the two bulging areas on either side of the fish’s head, which are destined to become eyes and skin, express keratin (red).

Oscar Ruiz, who works in the lab of George Eisenhoffer at The University of Texas MD Anderson Cancer Center, Houston, used a confocal microscope to create this image. What was most innovative about his work was not the microscope itself, but how he prepared the sample for imaging. With traditional methods, researchers can only image the faces of zebrafish larvae from the side or the bottom. However, the Eisenhoffer lab has devised a new method of preparing fish larvae that makes it possible to image their faces head-on. This has enabled the team to visualize facial development at much higher resolution than was previously possible.

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Stem Cell Research: New Recipes for Regenerative Medicine

Cartilage and bone formation from stem cells

Caption: From stem cells to bone. Human bone cell progenitors, derived from stem cells, were injected under the skin of mice and formed mineralized structures containing cartilage (1-2) and bone (3).
Credit: Loh KM and Chen A et al., 2016

To help people suffering from a wide array of injuries and degenerative diseases, scientists and bioengineers have long dreamed of creating new joints and organs using human stem cells. A major hurdle on the path to achieving this dream has been finding ways to steer stem cells into differentiating into all of the various types of cells needed to build these replacement parts in a fast, efficient manner.

Now, an NIH-funded team of researchers has reported important progress on this front. The researchers have identified for the first time the precise biochemical signals needed to spur human embryonic stem cells to produce 12 key types of cells, and to do so rapidly. With these biochemical “recipes” in hand, researchers say they should be able to generate pure populations of replacement cells in a matter of days, rather than the weeks or even months it currently takes. In fact, they have already demonstrated that their high-efficiency approach can be used to produce potentially therapeutic amounts of human bone, cartilage, and heart tissue within a very short time frame.

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Snapshots of Life: Arabidopsis Art

Arabidopsis

Credit: Nathanaël Prunet, California Institute of Technology, Pasadena

Modern sculptors might want to take a few notes from Mother Nature. The striking, stone-like forms that you see above are a micrograph of flower buds from the mustard plant Arabidopsis thaliana, which serves as an important model organism in biomedical research. In the center are the shoot apical meristems, consisting of undifferentiated stem cells (gray) that give rise to the flowers. Around the edge are buds that are several hours older, in which the flowers have just begun to form off of the shoot apical meristems. And, to the bottom left, are four structures that are the early sepals that will surround the fully formed flower that will bloom in a few weeks. The colored circles indicate areas of gene activity involved in determining the gender of the resulting flower, with masculinizing genes marked in green and feminizing in red.

This image, a winner in the Federation of American Societies for Experimental Biology’s 2015 BioArt competition, is the creation of postdoctoral student Nathanaёl Prunet, now in the NIH-supported lab of Elliot Meyerowitz at the California Institute of Technology, Pasadena, CA. Using scanning electron microscopy, Prunet snapped multiple 2D photographs of Arabidopsis buds at different tissue depths and computationally combined them to produce this 3D image.

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