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MBC in Press, published online ahead of print April 26, 2006
Mol. Biol. Cell 10.1091/mbc.E05-11-1087

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Submitted on November 30, 2005
Revised on March 30, 2006
Accepted on April 14, 2006

Cell Aggregation-induced FGF8 Elevation Is Essential for P19 Cell Neural Differentiation

Chen Wang,* Caihong Xia,* Wei Bian,* Li Liu,* Wei Lin,*{dagger} Ye-Guang Chen,{ddagger} Siew-Lan Ang,{dagger} and Naihe Jing*

*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; {dagger}Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom; {ddagger}Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China

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 inhibition-independent role in P19 cell neural differentiation.

Address correspondence to: Naihe Jing (njing{at}sibs.ac.cn)




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