PUBLICATION
The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential
- Authors
- Morabito, R.M., Tatarakis, D., Swick, R., Stettnisch, S., Nayak, P.K., Schilling, T.F., Horsfield, J.A., Martin, B.L.
- ID
- ZDB-PUB-251011-3
- Date
- 2025
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Horsfield, Jules, Martin, Benjamin, Schilling, Tom
- Keywords
- Auxin inducible degron, Floor plate, Neuromesodermal progenitors, Notochord, Single cell sequencing, Sox2, Wnt
- Datasets
- GEO:GSE171482
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Differentiation
- Gene Expression Regulation, Developmental
- Mesoderm*/cytology
- Mesoderm*/embryology
- Mesoderm*/metabolism
- Notochord/cytology
- Notochord/embryology
- Notochord/metabolism
- SOX Transcription Factors
- SOXB1 Transcription Factors*/genetics
- SOXB1 Transcription Factors*/metabolism
- Spinal Cord/cytology
- Spinal Cord/embryology
- Spinal Cord/metabolism
- Wnt Signaling Pathway*/physiology
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41071681 Full text @ Development
Citation
Morabito, R.M., Tatarakis, D., Swick, R., Stettnisch, S., Nayak, P.K., Schilling, T.F., Horsfield, J.A., Martin, B.L. (2025) The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential. Development (Cambridge, England). :.
Abstract
Neuromesodermal progenitors (NMPs) are a vertebrate cell type that contribute descendants to both the spinal cord and the mesoderm. The undifferentiated bipotential NMP state is maintained when both Wnt signaling is active and Sox2 is present. We used transgenic reporter lines to live-image both Wnt activity and Sox2 levels in NMPs and observed a unique cellular ratio in NMPs compared to NMP-derived mesoderm or neural tissue. We used this unique signature to identify the previously unknown anatomical position of a progenitor population that gives rise to midline tissues of the floor plate of the spinal cord and the mesodermal notochord. Thus, quantification of the active Wnt signaling to Sox2 ratio can be used to predict and identify cells with neuromesodermal potential. We also developed the auxin inducible 2 degron system for use in zebrafish to test the temporal role that Sox2 plays during midline formation. We found ectopic Sox2 in the presence of Wnt activity holds cells in the undifferentiated floor plate/notochord progenitor state, and that degradation of the ectopic Sox2 is required for cells to adopt a notochord fate.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping