A new technique for watching the developing embryo has led to insights into how a homogeneous ball of cells transforms into an embryo with different types of tissues.
In the normal zebrafish embryo, certain signaling molecules make sure the ball of cells turns into more than just a bigger ball of cells: They tell different parts of the embryo to turn into different types of tissue, such as muscle, brain, skin and bones. The molecules, called cyclops and squint, because fish lacking these proteins develop with fused eyes (and a host of other severe abnormalities), act through a protein called Smad2 that transcribes genes specific to these different types of tissue.
Researchers Steven Harvey of the University of Cambridge and James Smith of the National Institute for Medical Research in London wanted to know how the same signals could make one embryonic cell develop into heart cells while turning another into the lining of the lungs.
To visualize the process, Harvey and Smith fused Smad2 to a fluorescent yellow protein called Venus. They hacked Venus such that it would only glow when Smad2 was activated and thus capable of transcribing a gene.
By quantifying their Smad2 beacon, Harvey and Smith found that the concentration of signaling molecules was determining the different cell types: Low concentrations of the signals made cells become skin and nervous tissue, while higher concentrations resulted in muscle and internal organs. Although this had been hypothesized, it had been difficult to prove without this visualization technique.
Harvey and Smith also discovered the signals aren’t just important for different tissue types, but also determine which part of the embryo becomes the top and which becomes the bottom.
In the video, he cells in the zebrafish embryo shine brightly when a signal activates specific genes, which determine the cell’s eventual fate as part of a heart, brain, or other type of tissue. By analyzing the location, timing and brightness of the signal. Citation: “Visualisation and Quantification of Morphogen Gradient Formation in the Zebrafish” by Steven A. Harvey and James C. Smith. PLoS Biology, 7(5): e1000101. doi:10.1371/journal.pbio.1000101
