Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT-Induced Presomitic Mesoderm
| Autor: | Bernhard G. Herrmann, Anna D. Senft, Jinhua Liu, Frederic Koch, Phillip Grote, Matthias Marks, Lars Wittler, Anna Anurin, Smita Sudheer, Manuela Scholze, Karol Macura |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mesoderm Fibroblast Growth Factor 8 TBX6 Nodal signaling Mice Transgenic Biology Ligands Models Biological FGF and mesoderm formation 03 medical and health sciences Basic Helix-Loop-Helix Transcription Factors medicine Paraxial mesoderm Animals Humans Extracellular Signal-Regulated MAP Kinases Cells Cultured Genetics fungi Wnt signaling pathway Cell Differentiation Cell Biology Activins Cell biology Mice Inbred C57BL Wnt Proteins 030104 developmental biology medicine.anatomical_structure Somites Molecular Medicine Fibroblast Growth Factor 2 NODAL Intermediate mesoderm Developmental Biology |
| Zdroj: | Stem Cells. 34:1790-1800 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2371 |
| Popis: | Presomitic mesoderm (PSM) cells are the precursors of the somites, which flank both sides of the neural tube and give rise to the musculo-skeletal system shaping the vertebrate body. WNT and FGF signaling control the formation of both the PSM and the somites and show a graded distribution with highest levels in the posterior PSM. We have used reporters for the mesoderm/PSM control genes T, Tbx6, and Msgn1 to investigate the differentiation of mouse ESCs from the naïve state via EpiSCs to PSM cells. Here we show that the activation of WNT signaling by CHIR99021 (CH) in combination with FGF ligand induces embryo-like PSM at high efficiency. By varying the FGF ligand concentration, the state of PSM cells formed can be altered. High FGF concentration supports posterior PSM formation, whereas low FGF generates anterior/differentiating PSM, in line with in vivo data. Furthermore, the level of Msgn1 expression depends on the FGF ligand concentration. We also show that Activin/Nodal signaling inhibits CH-mediated PSM induction in EpiSCs, without affecting T-expression. Inversely, Activin/Nodal inhibition enhances PSM induction by WNT/high FGF signaling. The ability to generate PSM cells of either posterior or anterior PSM identity with high efficiency in vitro will promote the investigation of the gene regulatory networks controlling the formation of nascent PSM cells and their switch to differentiating/somitic paraxial mesoderm. |
| Databáze: | OpenAIRE |
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