PUBLICATION
Wnt signaling and tbx16 form a bistable switch to commit bipotential progenitors to mesoderm
- Authors
- Bouldin, C.M., Manning, A.J., Peng, Y.H., Farr, G.H., Hung, K.L., Dong, A., Kimelman, D.
- ID
- ZDB-PUB-150723-5
- Date
- 2015
- Source
- Development (Cambridge, England) 142: 2499-507 (Journal)
- Registered Authors
- Farr III, G. Hank, Kimelman, David
- Keywords
- Bipotential, Neuromesodermal, Somitogenesis, Spadetail, Tbx16, Wnt
- MeSH Terms
-
- Oligonucleotides/chemistry
- Mesoderm/metabolism*
- Muscles/embryology
- Muscles/metabolism
- Cell Movement
- Mice
- Body Patterning
- Wnt3A Protein/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism*
- Microscopy, Fluorescence
- Cell Differentiation
- Wnt Signaling Pathway*
- Neurons/metabolism
- Promoter Regions, Genetic
- Transgenes
- Animals
- Heat-Shock Proteins/metabolism
- T-Box Domain Proteins/metabolism*
- Gene Expression Regulation, Developmental*
- Cell Lineage
- Stem Cells/cytology
- In Situ Hybridization
- PubMed
- 26062939 Full text @ Development
Citation
Bouldin, C.M., Manning, A.J., Peng, Y.H., Farr, G.H., Hung, K.L., Dong, A., Kimelman, D. (2015) Wnt signaling and tbx16 form a bistable switch to commit bipotential progenitors to mesoderm. Development (Cambridge, England). 142:2499-507.
Abstract
Anterior to posterior growth of the vertebrate body is fueled by a posteriorly located population of bipotential neuro-mesodermal progenitor cells. These progenitors have a limited rate of proliferation and their maintenance is crucial for completion of the anterior-posterior axis. How they leave the progenitor state and commit to differentiation is largely unknown, in part because widespread modulation of factors essential for this process causes organism-wide effects. Using a novel assay, we show that zebrafish Tbx16 (Spadetail) is capable of advancing mesodermal differentiation cell-autonomously. Tbx16 locks cells into the mesodermal state by not only activating downstream mesodermal genes, but also by repressing bipotential progenitor genes, in part through a direct repression of sox2. We demonstrate that tbx16 is activated as cells move from an intermediate Wnt environment to a high Wnt environment, and show that Wnt signaling activates the tbx16 promoter. Importantly, high-level Wnt signaling is able to accelerate mesodermal differentiation cell-autonomously, just as we observe with Tbx16. Finally, because our assay for mesodermal commitment is quantitative we are able to show that the acceleration of mesodermal differentiation is surprisingly incomplete, implicating a potential separation of cell movement and differentiation during this process. Together, our data suggest a model in which high levels of Wnt signaling induce a transition to mesoderm by directly activating tbx16, which in turn acts to irreversibly flip a bistable switch, leading to maintenance of the mesodermal fate and repression of the bipotential progenitor state, even as cells leave the initial high-Wnt environment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping