Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 179, Issue 2-3, Pages 375-385Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2008.12.007
Keywords
Mouse embryonic stem cells; Icaritin; Neurogenesis; Choline acetyltransferase; Estrogen receptor; Fgf5; p38MAPK phosphorylation
Funding
- National Natural Sciences Foundation of China [90813026, 30672564, 30600762, 30472112, 30171121]
- Zhejiang Province [2006C13075, 2003C24005]
- Chinese ministry of Education [03088]
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A previous small molecule screen demonstrated that some prenylflavonoids can promote neuronal differentiation from mouse embryonic stem (ES) cells based on morphologic criteria. Here we build on this observation and examine the neuronal subtypes induced by icaritin, a compound screened, and the molecular events underlying the differentiation. In the presence of icaritin. the number of neural rosettes in embryoid bodies (EBs) expressing nestin efficiently increased and the neuroectodermal gene Fgf5 expression upregulated during germ layer formation. The neural progenitors generated from icaritin-treated EBs were further differentiated into the neurons (marked by beta-tubulin III) and also enhanced the choline acetyltransferase (ChAT) expression upon terminal differentiation. A suppression of p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and sustained extracellular signal-regulated protein kinase (ERK) phosphorylation existed simultaneously without estrogen-like activities involved. Taken together, enhanced co-expression of beta-tubulin III and choline acetyltransferase in neuronal differentiation from mouse ES cells is promoted by icaritin via estrogen receptor-independent action. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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