Feedback Forms Frogs

See allHide authors and affiliations

Science  08 Jul 2011:
Vol. 333, Issue 6039, pp. 138
DOI: 10.1126/science.333.6039.138-b

Signaling by gradients of the morphogen BMP (bone morphogenetic protein) controls the contributions of individual cells to the developing embryo. Genes encoding components of the BMP signaling pathway are expressed together in groups that include both components that favor BMP signaling and also feedback inhibitors of the pathway. Paulsen et al. used a combination of experiments and mathematical modeling to explore what advantage this organization of the BMP signaling module might confer. Human embryonic kidney cells responded to a range of BMP concentrations that varied almost 100-fold. But when a feedback inhibitor was removed, the dynamic range of response was reduced by a factor of 10. Another important role of the feedback inhibition was to reduce cell-to-cell variation in the response to BMP. Indeed, in Xenopus tadpoles, loss of feedback inhibitors led to a several-fold increase in variability in tail length during development. Thus, this developmental regulatory system is optimized to promote a robust, relatively constant phenotype in the face of genetic, environmental, and stochastic variation or noise.

Proc. Natl. Acad. Sci. U.S.A. 108, 10202 (2011).

Navigate This Article