Open AccessRatio of Wnt3a to BMP4 doses is critical to their synergistic effects on proliferation of differentiating mouse embryonic stem cells
Author(s) -
Lin S.Y.,
Chen C.L.,
Wu Y.L.,
Yang Y.C.,
Hwu Y.M.
Publication year - 2008
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2008.00535.x
Subject(s) - wnt3a , wnt signaling pathway , embryonic stem cell , p38 mitogen activated protein kinases , microbiology and biotechnology , kinase , bone morphogenetic protein 4 , stem cell , signal transduction , biology , chemistry , protein kinase a , biochemistry , gene
. 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 mESC 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.