Wnt signaling and tbx16 form a bistable switch to commit bipotential progenitors to mesoderm

43Citations
Citations of this article
109Readers
Mendeley users who have this article in their library.

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.Howthey 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 cellautonomously, 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 inwhich high levels ofWnt signaling induce atransition tomesodermby 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.

References Powered by Scopus

Self-perpetuating states in signal transduction: Positive feedback, double-negative feedback and bistability

911Citations
N/AReaders
Get full text

Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation

486Citations
N/AReaders
Get full text

Identification of a functional transposase of the Tol2 element, an Ac-like element from the Japanese medaka fish, and its transposition in the zebrafish germ lineage

403Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Transition states and cell fate decisions in epigenetic landscapes

278Citations
N/AReaders
Get full text

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development

154Citations
N/AReaders
Get full text

Position-dependent plasticity of distinct progenitor types in the primitive streak

139Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

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), 142(14), 2499–2507. https://doi.org/10.1242/dev.124024

Readers over time

‘15‘16‘17‘18‘19‘20‘21‘22‘23‘24‘2505101520

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 34

52%

Researcher 24

37%

Professor / Associate Prof. 7

11%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 36

49%

Agricultural and Biological Sciences 35

47%

Neuroscience 2

3%

Pharmacology, Toxicology and Pharmaceut... 1

1%

Save time finding and organizing research with Mendeley

Sign up for free
0