Müller, P., Rogers, K.W., Jordan, B.M., Lee, J.S., Robson, D., Ramanathan, S., Schier, A.F. (2012) Differential Diffusivity of Nodal and Lefty Underlies a Reaction-Diffusion Patterning System. Science (New York, N.Y.). 336(6082):721-724.
Biological systems involving short-range activators and long-range inhibitors can generate complex patterns. Reaction-diffusion
models postulate that differences in signaling range are caused by differential diffusivity of inhibitor and activator. Other
models suggest that differential clearance underlies different signaling ranges. To test these models, we measured the biophysical
properties of the Nodal/Lefty activator/inhibitor system during zebrafish embryogenesis. Analysis of Nodal and Lefty gradients
reveals that Nodals have a shorter range than Lefty proteins. Pulse-labeling analysis indicates that Nodals and Leftys have
similar clearance kinetics, whereas fluorescence recovery assays reveal that Leftys have a higher effective diffusion coefficient
than Nodals. These results indicate that differential diffusivity is the major determinant of the differences in Nodal/Lefty
range and provide biophysical support for reaction-diffusion models of activator/inhibitor-mediated patterning.