The signals of FGFs on the neurogenesis of embryonic stem cells.
BACKGROUND
Neural induction is a complex process and the detailed mechanism of FGF-induced neurogenesis remains unclear.


METHODS
By using a serum-free neural induction method, we showed that FGF1 dose-dependently promoted the induction of Sox1/N-cadherin/nestin triple positive cells, which represent primitive neuroblasts, from mouse embryonic stem (ES) cells.


RESULTS
We demonstrated that FGF1, FGF2, and FGF4, but not FGF8b, enhanced this neurogenesis. Especially, FGF-enhanced neurogenesis is not mediated through the rescue of the apoptosis or the enhancement of the proliferation of Sox1+ cells. We further indicated that the inactivation of c-Jun N-terminal kinase-1 (JNK-1) and extracellular signal-related kinase-2 (ERK-2), but not p38 mitogen-activated protein kinase (MAPK), inhibited the neural formation through the inhibition of ES differentiation, but not through the formation of endomesodermal cells.


CONCLUSIONS
These lines of evidence delineated the roles of FGF downstream signals in the early neural differentiation of ES cells.
Chen
Ching-Wen
CW
Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.
Liu
Chin-San
CS
Chiu
Ing-Ming
IM
Shen
Shih-Cheng
SC
Pan
Hung-Chuan
HC
Lee
Kun-Hsiung
KH
Lin
Shinn-Zong
SZ
Su
Hong-Lin
HL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D016895:Culture Media, Serum-Free; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D016895:Culture Media, Serum-Free; D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse; D005346:Fibroblast Growth Factors