Retinoic acid induces discrete Wnt-signaling-dependent differentiation in F9 cells.
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 beta-catenin, on the differentiation of F9 cells and beta-catenin-deficient F9 cells (betaT cells). RA up-regulated the expression of differentiation markers for primitive, visceral and parietal endoderm in F9 cells but not for visceral endoderm in betaT cells. Wnt3a or leukemia inhibitory factor (LIF) inhibited the RA-induced differentiation in F9 cells. LIF but not Wnt3a could inhibit differentiation in betaT cells. RA evoked ZO-1alpha+ 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 beta-catenin, and beta-catenin might be necessary in the process leading from primitive to visceral endoderm in F9 cells.
Inoue
Atsuko
A
Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan. ainoue@fupharm.fukuyama-u.ac.jp
Nagafuchi
Akira
A
Kikuchi
Akira
A
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004707:Endoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000378:metabolism*
D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D014212:Tretinoin