Quantitative imaging in whole-mount zebrafish embryos traces morphogen gradient maintenance and noise propagation in BMP signaling

Dorsoventral (DV) embryonic patterning relies on precisely controlled interpretation of morphogen signaling. In all vertebrates, DV axis specification is informed by gradients of Bone Morphogenetic Proteins (BMPs). We developed a 3D single-molecule mRNA quantification method in whole-mount zebrafish to quantify the inputs and outputs in this pathway. In combination with 3D computational modeling of zebrafish embryo development, data from this method revealed that Sizzled (Szl), shaped by BMP and Nodal signaling, kept a consistent inhibition level with Chordin (Chd) to maintain the BMP morphogen gradient. Intriguingly, BMP morphogen intrinsic expression is highly noisy at the ventral marginal layer in early zebrafish gastrula, where the gradient for DV patterning is established, which implies an unexpected role for noise in gradient shaping.