FGF2 and insulin signaling converge to regulate cyclin D expression in multipotent neural stem cells
Faculty Advisor
Dan Hoeppner, MD (Johns Hopkins Medical School, Lieber Institute for Brain Development)UMass Chan Affiliations
School of MedicineDocument Type
Journal ArticlePublication Date
2014-03-01Keywords
AnimalsCell Proliferation
Cyclin D
DNA
Female
Fibroblast Growth Factor 2
Insulin
Intracellular Space
Mice
Mice, Inbred C57BL
Models, Biological
Multipotent Stem Cells
Neural Stem Cells
Protein Biosynthesis
Proto-Oncogene Proteins c-fos
Proto-Oncogene Proteins c-jun
Signal Transduction
Transcription, Genetic
Cell Biology
Developmental Biology
Developmental Neuroscience
Molecular and Cellular Neuroscience
Metadata
Show full item recordAbstract
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.Source
Stem Cells. 2014 Mar;32(3):770-8. doi: 10.1002/stem.1575. Link to article on publisher's siteDOI
10.1002/stem.1575Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49258PubMed ID
24155149Notes
Medical student Adedamola Adepoju participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/stem.1575