Morphogen gradients are regulated by porous media characteristics of the developing tissue

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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 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.

Details

Original languageEnglish
Article numberdev204312
JournalDevelopment (Cambridge, England)
Volume152
Issue number13
Early online date2 Jun 2025
Publication statusPublished - Jul 2025
Peer-reviewedYes

External IDs

ORCID /0000-0003-4414-4340/work/186183018
unpaywall 10.1242/dev.204312
Scopus 105010590157

Keywords

Keywords

  • Animals, Computer Simulation, Diffusion, Embryo, Nonmammalian/metabolism, Extracellular Matrix/metabolism, Fibroblast Growth Factors/metabolism, Models, Biological, Morphogenesis, Porosity, Zebrafish Proteins/metabolism, Zebrafish/embryology