Abstract
The mGlu5 receptor is the only metabotropic glutamate receptor subtype expressed by mouse embryonic stem (ES) cells grown under non-differentiating conditions [Cappuccio, I., Spinanti, P. Porcellini, A., Desiderati, F., De Vita, T., Storto, M., Capobianco, L., Battaglia, G., Nicoletti, F., Melchiorri, D., 2005. Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells. Neuropharmacology 1, 196-205]. We now report that ES cells differentiating into embryoid bodies (EBs) progressively lose mGlu5 receptors and begin to express mGlu4 receptors at both mRNA and proteinc level. A 4-day treatment of EBs with the mGlu4 receptor agonist, l-2-amino-4-phosphonobutanoate (l-AP4), increased mRNA levels of the mesoderm marker, brachyury and the endoderm marker, H19, and decreased the expression of the transcript for the primitive ectoderm marker, fibroblast-growth factor-5 (FGF-5). These effects were prevented by the mGlu4 receptor antagonists, α-methylserine-O-phosphate (MSOP). Plating of EBs for 4 days in vitro in ITSFn medium induced cell differentiation towards a neural lineage, as reflected by the expression of the intermediate filament protein, nestin, and the homeobox protein, Dlx-2. Pharmacological activation of mGlu4 receptors during cell incubation in ITSFn medium increased the expression of both neural markers. Similar results were obtained when neural differentiation was induced by exposure of EBs to retinoic acid. These data suggest that differentiation of cultured ES cells is associated with changes in the expression pattern of mGlu receptors and that activation of mGlu4 receptors affects cell differentiation in a context-dependent manner.
| Original language | English |
|---|---|
| Pages (from-to) | 606-611 |
| Number of pages | 6 |
| Journal | Neuropharmacology |
| Volume | 51 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2006 |
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Keywords
- Differentiation
- Embryoid bodies
- Metabotropic glutamate receptors subtype4
- Mouse embryonic stem cells
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Drug Discovery
- Pharmacology
Cite this
Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors. / Cappuccio, Irene; Verani, Roberta; Spinsanti, Paola; Niccolini, Cristiano; Gradini, Roberto; Costantino, Santa; Nicoletti, Ferdinando; Melchiorri, Daniela.
In: Neuropharmacology, Vol. 51, No. 3, 09.2006, p. 606-611.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors
AU - Cappuccio, Irene
AU - Verani, Roberta
AU - Spinsanti, Paola
AU - Niccolini, Cristiano
AU - Gradini, Roberto
AU - Costantino, Santa
AU - Nicoletti, Ferdinando
AU - Melchiorri, Daniela
PY - 2006/9
Y1 - 2006/9
N2 - The mGlu5 receptor is the only metabotropic glutamate receptor subtype expressed by mouse embryonic stem (ES) cells grown under non-differentiating conditions [Cappuccio, I., Spinanti, P. Porcellini, A., Desiderati, F., De Vita, T., Storto, M., Capobianco, L., Battaglia, G., Nicoletti, F., Melchiorri, D., 2005. Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells. Neuropharmacology 1, 196-205]. We now report that ES cells differentiating into embryoid bodies (EBs) progressively lose mGlu5 receptors and begin to express mGlu4 receptors at both mRNA and proteinc level. A 4-day treatment of EBs with the mGlu4 receptor agonist, l-2-amino-4-phosphonobutanoate (l-AP4), increased mRNA levels of the mesoderm marker, brachyury and the endoderm marker, H19, and decreased the expression of the transcript for the primitive ectoderm marker, fibroblast-growth factor-5 (FGF-5). These effects were prevented by the mGlu4 receptor antagonists, α-methylserine-O-phosphate (MSOP). Plating of EBs for 4 days in vitro in ITSFn medium induced cell differentiation towards a neural lineage, as reflected by the expression of the intermediate filament protein, nestin, and the homeobox protein, Dlx-2. Pharmacological activation of mGlu4 receptors during cell incubation in ITSFn medium increased the expression of both neural markers. Similar results were obtained when neural differentiation was induced by exposure of EBs to retinoic acid. These data suggest that differentiation of cultured ES cells is associated with changes in the expression pattern of mGlu receptors and that activation of mGlu4 receptors affects cell differentiation in a context-dependent manner.
AB - The mGlu5 receptor is the only metabotropic glutamate receptor subtype expressed by mouse embryonic stem (ES) cells grown under non-differentiating conditions [Cappuccio, I., Spinanti, P. Porcellini, A., Desiderati, F., De Vita, T., Storto, M., Capobianco, L., Battaglia, G., Nicoletti, F., Melchiorri, D., 2005. Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells. Neuropharmacology 1, 196-205]. We now report that ES cells differentiating into embryoid bodies (EBs) progressively lose mGlu5 receptors and begin to express mGlu4 receptors at both mRNA and proteinc level. A 4-day treatment of EBs with the mGlu4 receptor agonist, l-2-amino-4-phosphonobutanoate (l-AP4), increased mRNA levels of the mesoderm marker, brachyury and the endoderm marker, H19, and decreased the expression of the transcript for the primitive ectoderm marker, fibroblast-growth factor-5 (FGF-5). These effects were prevented by the mGlu4 receptor antagonists, α-methylserine-O-phosphate (MSOP). Plating of EBs for 4 days in vitro in ITSFn medium induced cell differentiation towards a neural lineage, as reflected by the expression of the intermediate filament protein, nestin, and the homeobox protein, Dlx-2. Pharmacological activation of mGlu4 receptors during cell incubation in ITSFn medium increased the expression of both neural markers. Similar results were obtained when neural differentiation was induced by exposure of EBs to retinoic acid. These data suggest that differentiation of cultured ES cells is associated with changes in the expression pattern of mGlu receptors and that activation of mGlu4 receptors affects cell differentiation in a context-dependent manner.
KW - Differentiation
KW - Embryoid bodies
KW - Metabotropic glutamate receptors subtype4
KW - Mouse embryonic stem cells
UR - http://www.scopus.com/inward/record.url?scp=33747077157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747077157&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2006.05.007
DO - 10.1016/j.neuropharm.2006.05.007
M3 - Article
C2 - 16806298
AN - SCOPUS:33747077157
VL - 51
SP - 606
EP - 611
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 3
ER -