Retinoic acid induces discrete Wnt-signaling-dependent differentiation in F9 cells |
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Authors: | Atsuko Inoue Akira Nagafuchi |
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Affiliation: | a Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuencho-1, Fukuyama, Hiroshima 729-0292, Japan b Department of Cellular Interactions, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, 860-0811, Japan c Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan |
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Abstract: | Retinoic acid (RA) induces F9 cells, the mouse teratocarcinoma cells, to differentiate into primitive endoderm and further into visceral and parietal endoderm depending on the culture conditions. To elucidate the instructive mechanisms involved in the differentiation steps we investigated the effects of Wnt-signaling members, Wnt3a and β-catenin, on the differentiation of F9 cells and β-catenin-deficient F9 cells (βT cells). RA up-regulated the expression of differentiation markers for primitive, visceral and parietal endoderm in F9 cells but not for visceral endoderm in βT cells. Wnt3a or leukemia inhibitory factor (LIF) inhibited the RA-induced differentiation in F9 cells. LIF but not Wnt3a could inhibit differentiation in βT cells. RA evoked ZO-1α+ signals at cell-to-cell contacts in F9 cells in a Wnt3a sensitive manner. The results suggest that Wnt3a inhibits differentiation into endoderm through a pathway involving β-catenin, and β-catenin might be necessary in the process leading from primitive to visceral endoderm in F9 cells. |
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Keywords: | Differentiation F9 cells β-Catenin-deficient F9 cells Primitive endoderm Visceral endoderm Parietal endoderm Wnt3a β-Catenin Retinoic acid |
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