Wnt signaling andtbx16form a bistable switch to commit bipotential progenitors to mesoderm
| العنوان: | Wnt signaling andtbx16form a bistable switch to commit bipotential progenitors to mesoderm |
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| المؤلفون: | David Kimelman, King L. Hung, Alice X. Dong, Alyssa J. Manning, Cortney M. Bouldin, Gist H. Farr, Yu Hsuan Peng |
| المصدر: | Development. |
| بيانات النشر: | The Company of Biologists, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Mesoderm, animal structures, Cellular differentiation, Population, Oligonucleotides, Biology, Mice, Cell Movement, Wnt3A Protein, Somitogenesis, medicine, Animals, Cell Lineage, Transgenes, Progenitor cell, Promoter Regions, Genetic, education, Wnt Signaling Pathway, Molecular Biology, Zebrafish, Heat-Shock Proteins, In Situ Hybridization, Body Patterning, Neurons, Genetics, education.field_of_study, Muscles, Stem Cells, Wnt signaling pathway, Gene Expression Regulation, Developmental, Cell Differentiation, Zebrafish Proteins, biology.organism_classification, Cell biology, medicine.anatomical_structure, Microscopy, Fluorescence, embryonic structures, T-Box Domain Proteins, Research Article, Developmental Biology |
| الوصف: | Anterior to posterior growth of the vertebrate body is fueled by a posteriorly located population of bipotential neuro-mesodermal progenitor cells. These progenitor cells have a limited rate of proliferation, and their maintenance is critical for completion of the anterior-posterior axis. How these cells 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 Tbx16 (Spadetail) is capable of advancing mesodermal differentiation cell-autonomously. We find that 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 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. |
| تدمد: | 1477-9129 0950-1991 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31da34dfc08960f0eacae9a650330839 https://doi.org/10.1242/dev.124024 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....31da34dfc08960f0eacae9a650330839 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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