Stark Justina, Harish Rohit Krishnan, Sbalzarini Ivo F, Brand Michael
Dresden University of Technology, Faculty of Computer Science, Dresden 01187, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
Development. 2025 Jul 1;152(13). doi: 10.1242/dev.204312. Epub 2025 Jul 14.
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.
有人提出，长程形态发生素梯度是通过形态发生素从局部源扩散到靶组织中的分布式汇而形成的。然而，复杂组织几何结构在这一过程中的作用尚不太清楚，并且在现有模型中尚未得到明确解决。在这里，我们从光片显微镜图像中数值重建斑马鱼外包过程的孔隙尺度三维几何结构。在这些高分辨率的三维几何结构中，我们模拟了Fgf8a在曲折的细胞外空间中的梯度形成。我们的模拟表明，当考虑实际的胚胎几何结构时，一种与细胞外基质聚合物额外结合的源扩散降解机制足以解释Fgf8a梯度的出现和稳健维持。预测的归一化梯度对源和汇速率的变化具有鲁棒性，但对细胞外空间孔隙连通性的变化敏感，连通性较低会导致梯度更陡、更短。这证明了在研究形态发生素梯度时考虑实际几何结构的重要性。
