Evidence map›Paper›PMID 26062939›Full record

ArticleDevelopment (Cambridge, England)2015

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

Cortney M Bouldin, Alyssa J Manning, Yu-Hsuan Peng, Gist H Farr, King L Hung, Alice Dong, David Kimelman

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Article
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  11. Review
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  14. Article
  15. Overview of Secondary Neurulation.Journal of Korean Neurosurgical Society · 2021
    Article
  16. Article
  17. Fgf-driven Tbx protein activities directly induceDevelopment (Cambridge, England) · 2020
    Article
  18. Review
  19. Development (Cambridge, England) · 2019
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Cortney M BouldinDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alyssa J ManningDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Yu-Hsuan PengDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Gist H FarrDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
King L HungDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alice DongDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
David KimelmanDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA kimelman@uw.edu.

Funding

Regulation of Mesodermal Progenitors in Transgenic ZebrafishR01GM079203 · NIGMS · UNIVERSITY OF WASHINGTON · PI KIMELMAN, DAVID · 2008 to 2020
$4.0M
Regulation of proliferation in vertebrate embryonic mesodermal progenitorsF32GM099306 · NIGMS · UNIVERSITY OF WASHINGTON · PI BOULDIN, CORTNEY M · 2011 to 2013
$155k
NIGMS NIH HHS F32 GM099306NIGMS NIH HHS GM099306NIGMS NIH HHS R01 GM079203NIGMS NIH HHS R01GM079203
6 · The paper itself

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.

Indexed as

Gene Expression Regulation, DevelopmentalWnt Signaling PathwayAnimalsBody PatterningCell DifferentiationCell LineageCell MovementHeat-Shock ProteinsIn Situ HybridizationMesodermMiceMicroscopy, FluorescenceMusclesNeuronsOligonucleotidesPromoter Regions, GeneticHeat-Shock ProteinsOligonucleotidesT-Box Domain Proteinstbx16 protein, zebrafishWnt3A ProteinWnt3a protein, zebrafishZebrafish ProteinsBipotentialNeuromesodermalSomitogenesisSpadetailTbx16Wnt

Identifiers

PMID26062939
PMCPMC4510867

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.