All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways.
BACKGROUND
All-trans retinoic acid (RA) is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs), we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture.


RESULTS
Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF) signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK) pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation.


CONCLUSIONS
RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.
Lu
Jianfeng
J
Department of Molecular Genetics, Shanghai Medical School, Fudan University, Shanghai, PR China. healthygod_world@hotmail.com
Tan
Li
L
Li
Ping
P
Gao
Hui
H
Fang
Bo
B
Ye
Shoudong
S
Geng
Zhe
Z
Zheng
Ping
P
Song
Houyan
H
D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse; D051153:Wnt Proteins; D014212:Tretinoin; D048049:Extracellular Signal-Regulated MAP Kinases