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

Autor: Paola Spinsanti, I. Cappuccio, Roberto Gradini, Santa Costantino, Cristiano Niccolini, Daniela Melchiorri, Ferdinando Nicoletti, Roberta Verani
Rok vydání: 2006
Předmět:
Fetal Proteins
RNA
Untranslated
Fibroblast Growth Factor 5
Cellular differentiation
Glycine
Retinoic acid
Tretinoin
Ectoderm
Embryoid body
Biology
Receptors
Metabotropic Glutamate
Cell Line
Mice
Phosphoserine
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Excitatory Amino Acid Agonists
medicine
Animals
Drug Interactions
RNA
Messenger
Receptor
Homeodomain Proteins
Pharmacology
Analysis of Variance
Reverse Transcriptase Polymerase Chain Reaction
Aminobutyrates
Stem Cells
Gene Expression Regulation
Developmental
Cell Differentiation
Nestin
Embryo
Mammalian
Immunohistochemistry
Molecular biology
Embryonic stem cell
Cell biology
Adaptor Proteins
Vesicular Transport
differentiation
embryoid bodies
metabotropic glutamate receptors subtype4
mglu4
mouse embryonic stem cells
stem cell differentiation
medicine.anatomical_structure
chemistry
Metabotropic glutamate receptor
RNA
Long Noncoding
T-Box Domain Proteins
Excitatory Amino Acid Antagonists
Transcription Factors
Zdroj: Neuropharmacology. 51:606-611
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2006.05.007
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: