In groundbreaking experiments, Hans Spemann demonstrated that the dorsal part of the amphibian embryo can generate a well-proportioned tadpole, and that a small group of dorsal cells, the 'organizer', can induce a complete and well-proportioned twinned axis when transplanted into a host embryo. Key to organizer function is the localized secretion of inhibitors of bone morphogenetic protein (BMP), which defines a graded BMP activation profile. Although the central proteins involved in shaping this gradient are well characterized, their integrated function, and in particular how pattern scales with size, is not understood. Here we present evidence that in Xenopus, the BMP activity gradient is defined by a 'shuttling-based' mechanism, whereby the BMP ligands are translocated ventrally through their association with the BMP inhibitor Chordin. This shuttling, with feedback repression of the BMP ligand Admp, offers a quantitative explanation to Spemann's observations, and accounts naturally for the scaling of embryo pattern with its size.
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Acknowledgements We thank J. Christian for the BMP4 constructs, and the members of our groups for discussions and help with the experiments. This work was supported by Minerva, the Israel Science Foundation and the Hellen and Martin Kimmel award for innovative investigations to N.B. and a grant from the Israel Science Foundation and the Wolfson Family Chair in Genetics to A.F. B-Z.S. holds the Hilda and Cecil Lewis Professorial chair in Molecular Genetics.