Evaluation of BMP-mediated patterning in a 3D mathematical model of the zebrafish blastula embryo

Abstract

Bone Morphogenetic Proteins (BMPs) play an important role in dorsal-ventral (DV) patterning of the early zebrafish embryo. BMP signaling is regulated by a network of extracellular and intracellular factors that impact the range and signaling of BMP ligands. Recent advances in understanding the mechanism of pattern formation support a source-sink mechanism, however it is not clear how the source-sink mechanism shapes patterns in 3D, nor how sensitive the pattern is to biophysical rates and boundary conditions along both the anteroposterior (AP) and DV axes of the embryo. We propose a new three-dimensional growing Partial Differential Equation (PDE)-based model to simulate the BMP patterning process during the blastula stage. This model provides a starting point to elucidate how different mechanisms and components work together in 3D to create and maintain the BMP gradient in the embryo. We also show how the 3D model fits the BMP signaling gradient data at multiple time points along both axes. Furthermore, sensitivity analysis of the model suggests that the spatiotemporal patterns of Chordin and BMP ligand gene expression are dominant drivers of shape in 3D and more work is needed to quantify the spatiotemporal profiles of gene and protein expression to further refine the models.

Quantitative Imaging in Whole-mount Zebrafish Embryos Traces Morphogen Gradient Maintenance and Noise Propagation in BMP Signaling

“…DAPI was used at the last step to stain the nucleus, and the cells were mounted with Fluoromount-G (SouthernBiotech, Cat NO 0100-01). smFISH using RNAscope method on whole-mount embryos We used the protocol shown in our published paper (Li et al 2020). Detailed probe information and dilutions are shown in Table 3.…”

“…Our data implied that this mutual inhibition might play an essential role in BMP morphogen maintenance. To determine the impact of different szl expression on a three-dimensional level, we modi ed our previously built three-dimensional growing domain model, which includes the growth of epiboly and 3D patterning (Li et al 2020); the mathematical equations for this model are shown in Table 4. We adopted 182 sets of parameters screened from our 10 million 1D simulations (Tuazon et al 2020) and applied different expression regions of szl as simulation input, with margin (Fig.…”