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Science 336 (6082): 721-724

Copyright © 2012 by the American Association for the Advancement of Science

Differential Diffusivity of Nodal and Lefty Underlies a Reaction-Diffusion Patterning System

Patrick Müller,1,* Katherine W. Rogers,1 Ben M. Jordan,2,{dagger} Joon S. Lee,1,{dagger} Drew Robson,1 Sharad Ramanathan,1,3 Alexander F. Schier1,3,*

Abstract: 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 revealed that Nodals have a shorter range than Lefty proteins. Pulse-labeling analysis indicated that Nodals and Leftys have similar clearance kinetics, whereas fluorescence recovery assays revealed 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.

1 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
2 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
3 FAS Center for Systems Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.

{dagger} These authors contributed equally to this work.

* To whom correspondence should be addressed. E-mail: pmueller{at} (P.M.); schier{at} (A.F.S.)

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