title: Cell aggregation-induced FGF8 elevation is essential for P19 cell neural differentiation.
abstract: 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.
authors.affiliation: Key Laboratory of Stem 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.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Caihong
authors.initials: C
authors.lastname: Xia
authors.forename: Wei
authors.initials: W
authors.lastname: Bian
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
authors.forename: Siew-Lan
authors.initials: SL
authors.lastname: Ang
authors.forename: Naihe
authors.initials: N
authors.lastname: Jing
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D018236:Carcinoma, Embryonal; D002449:Cell Aggregation; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D051524:Fibroblast Growth Factor 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction; D051905:Smad6 Protein / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019485:Bone Morphogenetic Proteins; C496457:Fgf8 protein, mouse; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D034741:RNA, Small Interfering; C105686:SU 5402; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D051524:Fibroblast Growth Factor 8