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., Čapek, 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
-
- Animals
- Diffusion
- Gene Expression Regulation, Developmental
- Left-Right Determination Factors/genetics
- Nodal Protein*/metabolism
- Transforming Growth Factor beta/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- PubMed
- 36243734 Full text @ Nat. Commun.
Citation
Kuhn, T., Landge, A.N., Mörsdorf, D., Coßmann, J., Gerstenecker, J., Čapek, D., Müller, P., Gebhardt, J.C.M. (2022) Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model. Nature communications. 13:6101.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping