Zebrafish embryos show how cells communicate

26 October 2015

Early zebrafish embryo. The cells with bright green nuclei are those that have Nodal signalling.

Image: Early zebrafish embryo. The cells with bright green nuclei are those that have Nodal signalling.

Francis Crick Institute scientists have shed light on signalling between cells in developing embryos - by demonstrating a difference in timing of the production of a key morphogen (signalling protein) called Nodal and its inhibitor protein called Lefty. 

The study was carried out in zebrafish embryos. Zebrafish is a great model system as its embryos are completely transparent, meaning that researchers can use a microscope to watch development happening. In addition, 70 per cent of human genes also exist in zebrafish, so what they learn in zebrafish is applicable to humans.

Francis Crick Institute scientists have discovered how a key signalling molecule - a small protein called Nodal - generates the right number of cells that will become muscle, liver and other internal organs, at the right time, in a developing embryo. 

The researchers showed that the process is controlled by the timing of the production of Nodal and of its inhibitor protein, called Lefty.

Dr Caroline Hill of the Crick (currently based at Lincoln's Inn Fields) explained: "The cells that make up the tissues of the body can communicate with each other and instruct each other on what to do. How cells do this has fascinated scientists for decades because it is at the heart of how an entire organism can grow out from a single fertilised cell during embryonic development.

"Cell-to-cell communication is an important process in normal tissues, but it can also contribute to diseases like cancer when cells give or receive the wrong instructions."

An important way cells communicate is through the release of signalling molecules called morphogens. The small protein called Nodal is a key morphogen in the developing embryo. Nodal is found in all animals - from sponges to humans. Without it, humans do not form muscle or internal organs such as the intestines, liver and pancreas.

The team studied zebrafish embryos in which they could visualise cells in which the Nodal signal was active. This showed them that Nodal does not move long distances away from the producing cells, as was previously assumed, but instead signals to adjacent cells, activating further Nodal production and thereby spreading.

Surprisingly, the production of Nodal's inhibiting protein Lefty, which had always been assumed to be present in cells at the same time as Nodal, was delayed. This delay created a window of opportunity for Nodal to activate production of more Nodal in neighbouring cells, allowing the signal to spread to more cells. However, over time the levels of Lefty gradually went up until its level was high enough to stop the Nodal signal from spreading further. The difference in timing of the production of Nodal and Lefty is therefore what determines how many cells will become muscle, liver or pancreas etc.

Dr Hill said: "These findings will contribute to understanding how embryonic development works, and may even change how scientists think about secreted signals in other healthy and diseased tissues.

"In the future, the work could lead to new strategies to prevent the progression of diseases such as cancer."

The paper,  A Temporal Window for Signal Activation Dictates the Dimensions of a Nodal Signaling Domain, is published in Developmental Cell.

 

  • Francis Crick Institute scientists have shed light on signalling between cells in developing embryos - by demonstrating a difference in timing of the production of a key morphogen (signalling protein) called Nodal and its inhibitor protein called Lefty.
  • The study was carried out in zebrafish embryos. Zebrafish is a great model system as its embryos are completely transparent, meaning that researchers can use a microscope to watch development happening. In addition, 70 per cent of human genes also exist in zebrafish, so what they learn in zebrafish is applicable to humans.
  • The work was supported by Cancer Research UK and the European Commission Network of Excellence EpiGeneSys.