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bioRxiv · 10.1101/2024.04.05.588250

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

Stark, J.·Harish, R. K.·Sbalzarini, I. F.·Brand, M.
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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 images. 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/588250v2_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@66c705org.highwire.dtl.DTLVardef@1943009org.highwire.dtl.DTLVardef@1dda6dcorg.highwire.dtl.DTLVardef@f5db66_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Stark, J., Harish, R. K., Sbalzarini, I. F., Brand, M.. 2024-04-06. Morphogen gradients are regulated by porous media characteristics of the developing tissue. https://doi.org/10.1101/2024.04.05.588250

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