PUBLICATION

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

Authors

Kuhn, T., Landge, A.N., Mörsdorf, D., Coßmann, J., Gerstenecker, J., ?apek, D., Müller, P., Gebhardt, J.C.M.

ID

ZDB-PUB-221018-84

Date

2022

Source

Nature communications 13: 6101 (Journal)

Registered Authors

Müller, Patrick

Keywords

none

MeSH Terms

Transforming Growth Factor beta/metabolism
Left-Right Determination Factors/genetics
Animals
Diffusion
Zebrafish Proteins/genetics
Gene Expression Regulation, Developmental
Nodal Protein*/metabolism
Zebrafish*/genetics

PubMed

36243734 Full text @ Nat. Commun.

Abstract

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.

Genes / Markers

Figures