Retinoic acid gradient visualized for the first time in an embryo

April 7, 2013
These are retinoic acid gradients in a zebrafish embryo, visualized using cyan and yellow fluorophores. Credit: RIKEN

In a ground-breaking study, researchers from the RIKEN Brain Science Institute in Japan report a new technique that allows them to visualize the distribution of retinoic acid in a live zebrafish embryo, in real-time. This technique enabled them to observe two concentration gradients going in opposing directions along the head-to-tail axis of the embryo, thus providing long-awaited evidence that retinoic acid is a morphogen.

The report, published today in the journal Nature, puts an end to a long-standing debate around the presence of retinoic acid gradients across the vertebrate embryo, during the early stages of development. It also sheds light on the role of retinoic acid in .

Retinoic acid has been thought to be a , a signalling molecule that diffuses throughout the embryo switching genes on and off and imparting different cell fates depending on its concentration. However, retinoic acid concentration gradients had never been visualized because retinoic acid cannot be tagged with the commonly used '' GFP, or GFP-like proteins, as label.

"Until now no one had succeeded in monitoring the concentration of retinoic acid in real-time in a live embryo, and there was no direct data proving the existence of a retinoic acid gradient in the vertebrate embryo, explains Dr. Miyawaki, who led the research.

In order to monitor the concentration of retinoic acid in live zebrafish embryos at the early stages of their development, Dr. Miyawaki and his colleague Dr. Shimozono developed a technique to tag the molecule that acts as receptor for retinoic acid with genetically-encoded, coloured fluorophores. Based on the principle of fluorescence (FRET), the tags allow them to visualize the presence of retinoic acid and quantitatively determine its concentration over time.

By combining this technique with pharmacological and genetic manipulations, Miyawaki and his team demonstrate the presence of two linear retinoic acid concentration gradients across the antero-posterior axis of the embryo, from the trunk area to the head and the tail. Their findings suggest that retinoic acid diffuses quickly, thus establishing stable and robust gradients that are resistant to external perturbations.

"A better understanding of the gradients of retinoic is essential for research into the patterns of tissue development. It is necessary if we ever want to control the development of three-dimensional tissue structures from induced pluripotent stem cells, for regenerative medicine for example," concludes Dr. Miyawaki.

Explore further: Link between prostate cancer and vitamin A may lead to improved treatment

Related Stories

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

A metabolic switch to turn off obesity

October 27, 2016

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...

Mitochondria control stem cell fate

October 27, 2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.