PUBLICATION
Optogenetic control of Nodal signaling patterns
- Authors
- McNamara, H.M., Guyer, A.M., Jia, B.Z., Parot, V.J., Dobbs, C.D., Schier, A.F., Cohen, A.E., Lord, N.D.
- ID
- ZDB-PUB-250328-14
- Date
- 2025
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Cohen, Adam, Schier, Alexander
- Keywords
- Gastrulation, Mesendodermal patterning, Morphogen, Nodal signaling, Optogenetics, Zebrafish
- MeSH Terms
-
- Embryo, Nonmammalian/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Cryptochromes/genetics
- Cryptochromes/metabolism
- Signal Transduction*/genetics
- Animals, Genetically Modified
- Optogenetics*/methods
- Animals
- Nodal Protein*/genetics
- Nodal Protein*/metabolism
- Gene Expression Regulation, Developmental
- PubMed
- 40145591 Full text @ Development
Citation
McNamara, H.M., Guyer, A.M., Jia, B.Z., Parot, V.J., Dobbs, C.D., Schier, A.F., Cohen, A.E., Lord, N.D. (2025) Optogenetic control of Nodal signaling patterns. Development (Cambridge, England). :.
Abstract
A crucial step in early embryogenesis is the establishment of spatial patterns of signaling activity. Tools to perturb morphogen signals with high resolution in space and time can help reveal how embryonic cells decode these signals to make appropriate fate decisions. Here, we present new optogenetic reagents and an experimental pipeline for creating designer Nodal signaling patterns in live zebrafish embryos. Nodal receptors were fused to the light-sensitive heterodimerizing pair Cry2/CIB1N, and the Type II receptor was sequestered to the cytosol. The improved optoNodal2 reagents eliminate dark activity and improve response kinetics, without sacrificing dynamic range. We adapted an ultra-widefield microscopy platform for parallel light patterning in up to 36 embryos and demonstrated precise spatial control over Nodal signaling activity and downstream gene expression. Patterned Nodal activation drove precisely controlled internalization of endodermal precursors. Further, we used patterned illumination to generate synthetic signaling patterns in Nodal signaling mutants, rescuing several characteristic developmental defects. This study establishes an experimental toolkit for systematic exploration of Nodal signaling patterns in live embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping