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Vol. 17, Issue 7, 3075-3084, July 2006
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*Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences and Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom; and
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
Submitted November 30, 2005;
Revised March 30, 2006;
Accepted April 14, 2006
Monitoring Editor: Marianne Bronner-Fraser
FGF8, a member of the fibroblast growth factor (FGF) family, has been shown to play important roles in different developing systems. Mouse embryonic carcinoma P19 cells could be induced by retinoic acid (RA) to differentiate into neuroectodermal cell lineages, and this process is cell aggregation dependent. In this report, we show that FGF8 expression is transiently up-regulated upon P19 cell aggregation, and the aggregation-dependent FGF8 elevation is pluripotent stem cell related. Overexpressing FGF8 promotes RA-induced monolayer P19 cell neural differentiation. Inhibition of FGF8 expression by RNA interference or blocking FGF signaling by the FGF receptor inhibitor, SU5402, attenuates neural differentiation of the P19 cell. Blocking the bone morphogenetic protein (BMP) pathway by overexpressing Smad6 in P19 cells, we also show that FGF signaling plays a BMP inhibitionindependent role in P19 cell neural differentiation.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Naihe Jing ( njing{at}sibs.ac.cn)
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