Objectives : To investigate potential interactions between bone morphogenetic protein (BMP) and Wnt signalling on differentiating mouse embryonic stem cells (mESC). Materials and methods : Mouse embryonic stem cells were cultured with differing combinations of Wnt3a, BMP4 and inhibitors of Wnt, BMP, PI-3K (phosphoinositide 3-kinase), p38, ERK1/2 (extracellular signal-regulated kinase 1/2) and JNK (c-Jun N-terminal kinase) pathways. Results : We found that Wnt3a synergized with BMP4 to promote

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... SC proliferation. Furthermore, the relative ratio of Wnt3a to BMP4 doses was critical to their synergistic effects, which could be abolished by using Dkk-1, noggin or the inhibitors of PI-3K, p38, ERK1/2 and JNK pathways. We also demonstrated that combination of Wnt3a and BMP4 could suppress ectodermal differentiation of mESCs. Moreover, inhibitors of PI-3K, p38, ERK1/2 and JNK pathways could negate this effect. Conclusion : Relative ratio of Wnt3a to BMP4 doses is critical to their synergistic effect on differentiating mESC proliferation, which may work through PI-3K, p38, ERK1/2 and JNK pathways.