Scaling of dorsal‐ventral patterning in the Xenopus laevis embryo

Abstract

Scaling of pattern with size has been described and studied for over a century, yet its molecular basis is understood in only a few cases. In a recent, elegant study, Inomata and colleagues proposed a new model explaining how bone morphogenic protein (BMP) activity gradient scales with embryo size in the early Xenopus laevis embryo. We discuss their results in conjunction with an alternative model we proposed previously. The expansion-repression mechanism (ExR) provides a conceptual framework unifying both mechanisms. Results of Inomata and colleagues implicate the chordin-stabilizing protein sizzled as the expander molecule enabling scaling, while we attributed this role to the BMP ligand Admp. The two expanders may work in concert, as suggested by the mathematical model of Inomata et al. We discuss approaches for differentiating the contribution of sizzled and Admp to pattern scaling.

Developmental Pattern Formation in Phases

“…This type of mechanism has been termed an 'Expander-repressor mechanism' [77,84] and has been proposed to act in several systems [85,86]. Recently, a complementary role for a protease, Sizzled, was revealed in this process [77,87]. These data suggested that scaling of the BMP activity gradient could be achieved by a combination of mechanisms [77].…”

“…Thus, ADMP can expand the BMP signalling activity, while BMP signalling simultaneously acts negatively on ADMP in a manner that depends on tissue size. This type of mechanism has been termed an 'Expander-repressor mechanism' [77,84] and has been proposed to act in several systems [85,86]. Recently, a complementary role for a protease, Sizzled, was revealed in this process [77,87].…”

“…To minimize such errors, initial patterns must be robust to variations in tissue size. In many systems, adjusting morphogen gradients to tissue size has been proposed to lead to scaling of the underlying pattern, and several mechanisms have been proposed [76][77][78]. Many studies addressing this issue have considered a simplified mechanism of morphogen interpretation, in which gene expression boundaries are positioned at defined morphogen concentrations.…”

BMP gradients: A paradigm for morphogen-mediated developmental patterning

“…The panoply of mechanistic experimental data summarized above has spurred development of increasingly complete and predictive mathematical models of BMP-mediated patterning (16,29,(55)(56)(57)(58). In several instances, these models have suggested potential new network behaviors that have subsequently been tested experimentally and verified.…”

“…2E) or Pentagone (Fig. 5B) in Drosophila wing discs [reviewed in (14,55)] provide examples of factors that can scale the gradient length constant to the growth of tissues. Expanders, which are typically produced at the low end of a gradient (by virtue of having their expression inhibited by morphogen signaling) and are highly diffusible, bind to ligands and stabilize them [e.g., by preventing their degradation (79)].…”