Decoding of position in the developing neural tube from antiparallel morphogen gradients

Building the neural tube The development of the neural tube is regulated by a pair of morphogens acting in opposing gradients. The mature neural tube is built from a variety of different cell types organized in a consistent dorsal-ventral pattern. Zagorski et al. asked how this pattern is defined in a reproducible way from individual to individual. The morphogens define positions most accurately toward the top of their respective gradients, but things get a bit messy in the middle. Modeling the gene regulatory network's response as a maximum likelihood estimation from the combined input of both morphogens, however, succeeds at defining even the intermediate positions. Thus, the computation of position by the gene regulatory network establishes accurate tissue patterning despite messy inputs. Science, this issue p. 1379 A gene regulatory network responds to noisy signals to build robustness and accuracy into tissue patterning during development. Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.