Robustness of patterning in zebrafish neural development

Abstract

Embryos develop robustly despite biological noise such as variation in size. How much variation can be tolerated and how scale invariance is achieved remain open questions. In this work, we studied scale invariance at the whole embryo and tissue level using single-cell genomics, genetic and molecular perturbations, and quantitative imaging in zebrafish embryos. We examined transcriptional responses and tissue proportion scaling in response to size perturbation in the whole embryo. We found relatively small changes in gene expression and that proportions of cell types largely scale. We also investigated how scale invariance is generated at the level of a single tissue, in the neural tube. We found evidence of a feedback network between Sonic Hedgehog (Shh), a key patterning molecule, and its regulator Scube2, in the ventral neural tube. We demonstrated that this feedback network is required for scaling the Shh gradient that patterns the ventral neural tube and used mathematical modeling to show that Scube2 feedback on release as well as diffusion of Shh enables the Shh gradient to be robust to differences in size. Patterning of progenitor domains in the ventral neural tube has long been studied. However, which signals and patterning mechanisms establish some of the other domains in the neural tube have been less explored, and how scaling may be achieved in these domains is less clear. To decipher the mechanisms that pattern the dorsal neural tube, we started to examine how patterning in the neural plate may impact cell fate decisions in the neural tube. We found that there is extensive patterning in the neural plate that is driven by multiple signals. Our results yield new insights into developmental patterning processes and provide data that can be used to further investigate mechanisms underlying developmental robustness.