Basic fibroblast growth factor endows dorsal telencephalic neural progenitors with the ability to differentiate into oligodendrocytes but not gamma-aminobutyric acidergic neurons.
Basic fibroblast growth factor (bFGF) is commonly used to enrich and maintain neural stem cells in vitro. Olig2 is an essential transcription factor for oligodendrocyte lineage specification and is expressed predominantly in ventral neuroepithelial cells in the medial and lateral ganglionic eminence (GE), where oligodendrocyte progenitors originate. Here we report significant induction of Olig2 expression in dorsal neuroepithelium-derived cells cultured in the presence of bFGF, in which Olig2-expressing cells were initially negligible. Among Olig2-expressing cells appearing after a 5-day treatment with bFGF, 99.8% coexpressed nestin. There was no significant difference in proliferation or apoptosis in dorsal and ventral neuroepithelial cultures in the presence of bFGF, suggesting that bFGF induces ectopic expression of Olig2 in dorsal "cortical" neuroepithelial cells. Similarly, expression of Mash1, another ventral neuroepithelial cell marker gene, was also induced in cultured dorsal neuroepithelial cells in the presence of bFGF. Conversely, in this culture, expression of dorsal neuroepithelial cell markers, such as Neurogenin1, Neurogenin2, Pax6, and Emx2, was down-regulated. These results suggested a possible ventralizing activity of bFGF. In fact, bFGF-treated dorsal neuroepithelial cells acquired the potential to generate O4-positive oligodendrocytes with efficacy comparable to that observed with GE-derived cells. In marked contrast, bFGF did not enable dorsal neuroepithelial cells to generate gamma-aminobutyric acid (GABA) neurons, which normally develop only from GE in vivo. Thus, bFGF endows dorsal telencephalic neural progenitors with the ability to differentiate into oligodendrocytes but not GABAergic neurons, suggesting the presence of different mechanisms governing specification of dorsoventral cell identities of neuronal and glial cell lineages.
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Masahiko
M
Abematsu
Tetsushi
T
Kagawa
Shinji
S
Fukuda
Toshihiro
T
Inoue
Hirohide
H
Takebayashi
Setsuro
S
Komiya
Tetsuya
T
Taga
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D005680:gamma-Aminobutyric Acid; C512773:Olig2 protein, mouse