Extracellular interactions and ligand degradation shape the nodal morphogen gradient

Animals develop from a single fertilized egg cell into multicellular organisms. This process requires chemical signals called “morphogens” that instruct the cells how to behave during development. The morphogens move across cells and tissues to form gradients of the signal. Cells then respond in different ways depending on how much of the signal they receive. This, in turn, depends on several factors: first, how quickly or slowly the signal moves; second, how well the morphogen binds to responding cells and other molecules in its path; and third, how much signal is lost or destroyed during the movement. Many researchers study morphogen gradients in the transparent zebrafish, since it grows quickly and it is easy to see developmental changes. However, until now it was not fully clear how the well-known morphogen called Nodal moves in live zebrafish as they develop. Wang, Wang et al. have now investigated how well Nodal signals bind to the surface of cells that receive the signal and to a molecule called “Lefty”, which is present in the same path and interferes with Nodal signals. Advanced techniques called fluorescence correlation and cross-correlation spectroscopy were used to measure Nodal signals at the level of single molecules in growing zebrafish. The experiments gave insights into how far Nodal signals move and remain active. The results showed that, in addition to Nodal diffusing and binding to receiving cells, one of the most important factors determining how far and quickly Nodal moves is its inactivation and destruction. Lastly, Wang, Wang et al. built computational models to test their observations from live zebrafish. The current work was based on forcing zebrafish to produce molecules including Nodal at locations within the fish that normally do not make them. Therefore future experiments will aim to examine these molecules and their interactions when they are produced at their normal locations in the animal over time.