Senior Scholars Program

Title

FGF2 and insulin signaling converge to regulate cyclin D expression in multipotent neural stem cells

UMMS Affiliation

School of Medicine

Faculty Advisor

Dan Hoeppner, MD (Johns Hopkins Medical School, Lieber Institute for Brain Development)

Date

3-2014

Document Type

Article

Medical Subject Headings

Animals; Cell 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

Disciplines

Cell Biology | Developmental Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience

Abstract

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.

Rights and Permissions

Citation: Stem Cells. 2014 Mar;32(3):770-8. doi: 10.1002/stem.1575. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Comments

Medical student Adedamola Adepoju participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.

PubMed ID

24155149