Open AccessFGF2 and Insulin Signaling Converge to Regulate Cyclin D Expression in Multipotent Neural Stem Cells
Author(s) -
Adepoju Adedamola,
Micali Nicola,
Ogawa Kazuya,
Hoeppner Daniel J.,
McKay Ronald D.G.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1575
Subject(s) - biology , multipotent stem cell , microbiology and biotechnology , neural stem cell , stem cell , pi3k/akt/mtor pathway , protein kinase b , neurosphere , receptor tyrosine kinase , signal transduction , cellular differentiation , adult stem cell , genetics , progenitor cell , gene
The ex vivo expansion of stem cells is making major contribution to biomedical research. The multipotent nature of neural precursors acutely isolated from the developing central nervous system has been established in a series of studies. Understanding the mechanisms regulating cell expansion in tissue culture would support their expanded use either in cell therapies or to define disease mechanisms. Basic fibroblast growth factor (FGF2) and insulin, ligands for tyrosine kinase receptors, are sufficient to sustain neural stem cells (NSCs) in culture. Interestingly, real‐time imaging shows that these cells become multipotent every time they are passaged. Here, we analyze the role of FGF2 and insulin in the brief period when multipotent cells are present. FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c‐Fos and c‐Jun that lead to elevated cyclin D mRNA levels. Insulin signals through the PI3k/Akt pathway to regulate cyclins at the post‐transcriptional level. This precise Boolean regulation extends our understanding of the proliferation of multipotent NSCs and provides a basis for further analysis of proliferation control in the cell states defined by real‐time mapping of the cell lineages that form the central nervous system. S tem C ells 2014;32:770–778