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Role of ERK 1/2 signaling in neuronal differentiation of cultured embryonic stem cells
Author(s) -
Li Zegui,
Theus Michelle Hedrick,
Wei Ling
Publication year - 2006
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2006.00889.x
Subject(s) - mapk/erk pathway , microbiology and biotechnology , biology , stem cell , embryonic stem cell , cellular differentiation , kinase , phosphorylation , retinoic acid , progenitor cell , neural stem cell , signal transduction , glial cell line derived neurotrophic factor , cell culture , neurotrophic factors , receptor , biochemistry , genetics , gene
Embryonic stem (ES) cells represent an ideal source for cell engraftment in the damaged central nervous system (CNS). Understanding key signals that control ES cell differentiation may improve cell type‐specific differentiation that is suitable for transplantation therapy. We tested the hypothesis that extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation is an early signaling event required for the neuronal differentiation of ES cells. Cultured mouse ES cells were treated with an all‐ trans ‐retinoic‐acid (RA) protocol to generate neurally induced progenitor cells. Western blot analysis showed a dramatic increase in ERK 1/2 phosphorylation (p‐ERK 1/2) 1–5 days after RA induction, which was attenuated in the presence of the p‐ERK 1/2‐specific inhibitor UO126. Phospho‐ERK 1/2 inhibition significantly reduced the number of NeuN‐positive cells and the expression of associated cytoskeletal proteins. In differentiating ES cells, there was increased nuclear translocation of STAT3 and decreased protein expression levels of GDNF, BDNF and NGF. STAT3 translocation was attenuated by UO126. Finally, caspase‐3 activation was observed in the presence of UO126, suggesting that the ERK pathway also contributes to the survival of differentiating ES cells. These data indicate that ERK 1/2 phosphorylation is a key event required for early neuronal differentiation and survival of ES cells.