Abstract
The aim of this study was to establish a cellular system to investigate the requirement for cell surface and diffusible molecules in the differentiation of fetal mesencephalic cells toward the dopamine lineage. Toward this end, we immortalized rat embryonic day 14 (E14) mesencephalon with a regulatable retroviral vector encoding v-myc. The stably transduced cells were pooled and designated as VME14 cells, VME14 cells proliferated rapidly, stopped proliferating, extended processes, and expressed GFAP after suppression of the v-myc expression with tetracycline, suggesting that VME14 cells differentiated into glial cells. Dissociated cells derived from the E11 rat mesencephalon gave rise to only a small number of tyrosine hydroxylase (TH)-positive neurons. However, when grown on a monolayer of the differentiated VME14 cells, a significantly higher number of cells differentiated into TH-positive neurons. VME14 cells were transduced with the secreted N-terminal cleavage product of the Sonic hedgehog gene (SHH-N), an inducer of mesencephalic dopaminergic neurons. This monoclonal, SHH-N-overexpressing cell line further enhanced dopaminergic differentiation of E11 rat mesencephalon cells. Thus, SHH-N and signals derived from fetal mesencephalic gila act cooperatively to facilitate dopaminergic differentiation. These fetal mesencephalon-derived cell lines will provide tools for the study of signals involved in dopaminergic differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 4326-4335 |
| Number of pages | 10 |
| Journal | Journal of Neuroscience |
| Volume | 21 |
| Issue number | 12 |
| Publication status | Published - Jun 15 2001 |
| Externally published | Yes |
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Keywords
- Differentiation
- Dopaminergic neuron
- Immortalization
- Mesencephalon
- Parkinson's disease
- Tyrosine hydroxylase
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Sonic hedgehog facilitates dopamine differentiation in the presence of a mesencephalic glial cell line. / Matsuura, N.; Lie, D. C.; Hoshimaru, M.; Asahi, M.; Hojo, M.; Ishizaki, R.; Hashimoto, N.; Noji, S.; Ohuchi, Hideyo; Yoshioka, H.; Gage, F. H.
In: Journal of Neuroscience, Vol. 21, No. 12, 15.06.2001, p. 4326-4335.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sonic hedgehog facilitates dopamine differentiation in the presence of a mesencephalic glial cell line
AU - Matsuura, N.
AU - Lie, D. C.
AU - Hoshimaru, M.
AU - Asahi, M.
AU - Hojo, M.
AU - Ishizaki, R.
AU - Hashimoto, N.
AU - Noji, S.
AU - Ohuchi, Hideyo
AU - Yoshioka, H.
AU - Gage, F. H.
PY - 2001/6/15
Y1 - 2001/6/15
N2 - The aim of this study was to establish a cellular system to investigate the requirement for cell surface and diffusible molecules in the differentiation of fetal mesencephalic cells toward the dopamine lineage. Toward this end, we immortalized rat embryonic day 14 (E14) mesencephalon with a regulatable retroviral vector encoding v-myc. The stably transduced cells were pooled and designated as VME14 cells, VME14 cells proliferated rapidly, stopped proliferating, extended processes, and expressed GFAP after suppression of the v-myc expression with tetracycline, suggesting that VME14 cells differentiated into glial cells. Dissociated cells derived from the E11 rat mesencephalon gave rise to only a small number of tyrosine hydroxylase (TH)-positive neurons. However, when grown on a monolayer of the differentiated VME14 cells, a significantly higher number of cells differentiated into TH-positive neurons. VME14 cells were transduced with the secreted N-terminal cleavage product of the Sonic hedgehog gene (SHH-N), an inducer of mesencephalic dopaminergic neurons. This monoclonal, SHH-N-overexpressing cell line further enhanced dopaminergic differentiation of E11 rat mesencephalon cells. Thus, SHH-N and signals derived from fetal mesencephalic gila act cooperatively to facilitate dopaminergic differentiation. These fetal mesencephalon-derived cell lines will provide tools for the study of signals involved in dopaminergic differentiation.
AB - The aim of this study was to establish a cellular system to investigate the requirement for cell surface and diffusible molecules in the differentiation of fetal mesencephalic cells toward the dopamine lineage. Toward this end, we immortalized rat embryonic day 14 (E14) mesencephalon with a regulatable retroviral vector encoding v-myc. The stably transduced cells were pooled and designated as VME14 cells, VME14 cells proliferated rapidly, stopped proliferating, extended processes, and expressed GFAP after suppression of the v-myc expression with tetracycline, suggesting that VME14 cells differentiated into glial cells. Dissociated cells derived from the E11 rat mesencephalon gave rise to only a small number of tyrosine hydroxylase (TH)-positive neurons. However, when grown on a monolayer of the differentiated VME14 cells, a significantly higher number of cells differentiated into TH-positive neurons. VME14 cells were transduced with the secreted N-terminal cleavage product of the Sonic hedgehog gene (SHH-N), an inducer of mesencephalic dopaminergic neurons. This monoclonal, SHH-N-overexpressing cell line further enhanced dopaminergic differentiation of E11 rat mesencephalon cells. Thus, SHH-N and signals derived from fetal mesencephalic gila act cooperatively to facilitate dopaminergic differentiation. These fetal mesencephalon-derived cell lines will provide tools for the study of signals involved in dopaminergic differentiation.
KW - Differentiation
KW - Dopaminergic neuron
KW - Immortalization
KW - Mesencephalon
KW - Parkinson's disease
KW - Tyrosine hydroxylase
UR - http://www.scopus.com/inward/record.url?scp=0035875674&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035875674&partnerID=8YFLogxK
M3 - Article
C2 - 11404418
AN - SCOPUS:0035875674
VL - 21
SP - 4326
EP - 4335
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 12
ER -