Scaling of the BMP activation gradient in Xenopus embryos

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. Development: How pattern scales with size The work of Hans Spemann in the early twentieth century was a seminal contribution to developmental biology, yet some aspects of his experiments are still unexplained at the molecular level. Most notably, the ability of dorsal-half embryos to regenerate a complete and well-proportionate (but smaller) axis indicates an unexplained capacity of embryos to scale pattern with size. Ben-Zvi et al . examined the graded distribution of BMP (bone morphogenetic protein) activity along the embryo that underlies the early dorsoventral patterning defined by an influential knot of cells known as Spemann's organizer. What emerges is a 'shuttling-based' mechanism, where BMP ligands are translocated ventrally through their association with the BMP inhibitor Chordin. This shuttling, coupled with feedback repression of the BMP ligand Admp, is used to quantitatively monitor embryo size and scale the activation gradient accordingly. In Xenopus , the bone morphogenetic protein (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 earlier observations, and accounts naturally for the scaling of embryo pattern with its size.