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Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model

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2022

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Landge, Amit N.
Mörsdorf, David
Coßmann, Jonas
Gerstenecker, Johanna
Gebhardt, J. Christof M.

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Nature Communications. Nature Publishing Group. 2022, 13, 6101. eISSN 2041-1723. Available under: doi: 10.1038/s41467-022-33704-z

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The hindered diffusion model postulates that the movement of a signaling molecule through an embryo is affected by tissue geometry and binding-mediated hindrance, but these effects have not been directly demonstrated in vivo. Here, we visualize extracellular movement and binding of individual molecules of the activator-inhibitor signaling pair Nodal and Lefty in live developing zebrafish embryos using reflected light-sheet microscopy. We observe that diffusion coefficients of molecules are high in extracellular cavities, whereas mobility is reduced and bound fractions are high within cell-cell interfaces. Counterintuitively, molecules nevertheless accumulate in cavities, which we attribute to the geometry of the extracellular space by agent-based simulations. We further find that Nodal has a larger bound fraction than Lefty and shows a binding time of tens of seconds. Together, our measurements and simulations provide direct support for the hindered diffusion model and yield insights into the nanometer-to-micrometer-scale mechanisms that lead to macroscopic signal dispersal.

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570 Biowissenschaften, Biologie

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ISO 690KUHN, Timo, Amit N. LANDGE, David MÖRSDORF, Jonas COSSMANN, Johanna GERSTENECKER, Daniel CAPEK, Patrick MÜLLER, J. Christof M. GEBHARDT, 2022. Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model. In: Nature Communications. Nature Publishing Group. 2022, 13, 6101. eISSN 2041-1723. Available under: doi: 10.1038/s41467-022-33704-z
BibTex
@article{Kuhn2022-10-15Singl-59023,
  year={2022},
  doi={10.1038/s41467-022-33704-z},
  title={Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model},
  volume={13},
  journal={Nature Communications},
  author={Kuhn, Timo and Landge, Amit N. and Mörsdorf, David and Coßmann, Jonas and Gerstenecker, Johanna and Capek, Daniel and Müller, Patrick and Gebhardt, J. Christof M.},
  note={Article Number: 6101}
}
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