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Media type:
E-Article
Title:
Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model
Contributor:
Kuhn, Timo;
Landge, Amit N.;
Mörsdorf, David;
Coßmann, Jonas;
Gerstenecker, Johanna;
Čapek, Daniel;
Müller, Patrick;
Gebhardt, J. Christof M.
Published:
Springer Science and Business Media LLC, 2022
Published in:
Nature Communications, 13 (2022) 1
Language:
English
DOI:
10.1038/s41467-022-33704-z
ISSN:
2041-1723
Origination:
Footnote:
Description:
AbstractThe 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.