Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors

Irene Cappuccio, Roberta Verani, Paola Spinsanti, Cristiano Niccolini, Roberto Gradini, Santa Costantino, Ferdinando Nicoletti, Daniela Melchiorri

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish
Pages (from-to)606-611
Number of pages6
JournalNeuropharmacology
Volume51
Issue number3
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Embryoid Bodies
Metabotropic Glutamate Receptors
Embryonic Stem Cells
Cell Differentiation
Fibroblast Growth Factor 5
Neuropharmacology
Homeodomain Proteins
Intermediate Filament Proteins
Nestin
Messenger RNA
Endoderm
Ectoderm
Mesoderm
Tretinoin
Pharmacology
Mouse Embryonic Stem Cells

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

Cappuccio, I., Verani, R., Spinsanti, P., Niccolini, C., Gradini, R., Costantino, S., ... Melchiorri, D. (2006). Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors. Neuropharmacology, 51(3), 606-611. https://doi.org/10.1016/j.neuropharm.2006.05.007

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 journalArticle

Cappuccio, I, Verani, R, Spinsanti, P, Niccolini, C, Gradini, R, Costantino, S, Nicoletti, F & Melchiorri, D 2006, 'Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors', Neuropharmacology, vol. 51, no. 3, pp. 606-611. https://doi.org/10.1016/j.neuropharm.2006.05.007
Cappuccio, Irene ; Verani, Roberta ; Spinsanti, Paola ; Niccolini, Cristiano ; Gradini, Roberto ; Costantino, Santa ; Nicoletti, Ferdinando ; Melchiorri, Daniela. / Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors. In: Neuropharmacology. 2006 ; Vol. 51, No. 3. pp. 606-611.
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