• 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.
  • Access State: Open Access