PUBLICATION
Morphogen gradients are regulated by porous media characteristics of the developing tissue
- Authors
- Stark, J., Harish, R.K., Sbalzarini, I.F., Brand, M.
- ID
- ZDB-PUB-250604-14
- Date
- 2025
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Brand, Michael
- Keywords
- Complex geometry, Epiboly, Extracellular space, Fibroblast growth factor, GPU-accelerated simulation, Gradient robustness, Image-based model, Morphogen gradient, Reaction-diffusion, Zebrafish
- MeSH Terms
-
- Animals
- Models, Biological
- Extracellular Matrix/metabolism
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Embryo, Nonmammalian/metabolism
- Porosity
- Fibroblast Growth Factors*/metabolism
- Zebrafish Proteins/metabolism
- Morphogenesis
- Computer Simulation
- Diffusion
- PubMed
- 40462756 Full text @ Development
Citation
Stark, J., Harish, R.K., Sbalzarini, I.F., Brand, M. (2025) Morphogen gradients are regulated by porous media characteristics of the developing tissue. Development (Cambridge, England). :.
Abstract
Long-range morphogen gradients have been proposed to form by morphogen diffusion from a localized source to distributed sinks in the target tissue. The role of the complex tissue geometry in this process is, however, less well understood and has not been explicitly resolved in existing models. Here, we numerically reconstruct pore-scale 3D geometries of zebrafish epiboly from light-sheet microscopy volumes. In these high-resolution 3D geometries, we simulate Fgf8a gradient formation in the tortuous extracellular space. Our simulations show that when realistic embryo geometries are considered, a source-diffusion-degradation mechanism with additional binding to extracellular matrix polymers is sufficient to explain self-organized emergence and robust maintenance of Fgf8a gradients. The predicted normalized gradient is robust against changes in source and sink rates but sensitive to changes in the pore connectivity of the extracellular space, with lower connectivity leading to steeper and shorter gradients. This demonstrates the importance of considering realistic geometries when studying morphogen gradients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping