title: Secreted factors from ventral telencephalon induce the differentiation of GABAergic neurons in cortical cultures.
abstract: It is widely believed that the pyramidal cells and interneurons of the cerebral cortex are distinct in their origin, lineage and genetic make up. In view of these findings, the current thesis is that the phenotype determination of cortical neurons is primarily directed by genetic mechanisms. Using in vitro assays, the present study demonstrates that secreted factors from ganglionic eminence (GE) of the ventral telencephalon have the potency to induce the differentiation of a subset of cortical neurons towards gamma-aminobutyric acid (GABA)ergic lineage. Characterization of cortical cultures that were exposed to medium derived from GE illustrated a significant increase in the number of GABA-, calretinin- and calbindin-positive neurons. Calcium imaging together with pharmacological studies showed that the application of exogenous medium significantly elevated the intracellular calcium transients in cortical neurons through the activation of ionotropic glutamate receptors. The increase in GABA+ neurons appeared to be associated with the elevated calcium activity; treatment with blockers specific for glutamate receptors abolished both the synchronized transients and reduced the differentiation of GABAergic neurons. Such studies demonstrate that although intrinsic mechanisms determine the fate of cortical interneurons, extrinsic factors have the potency to influence their neurochemical differentiation and contribute towards their molecular diversity.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: H-h
authors.initials: HH
authors.lastname: Trinh
authors.forename: J
authors.initials: J
authors.lastname: Reid
authors.forename: E
authors.initials: E
authors.lastname: Shin
authors.forename: A
authors.initials: A
authors.lastname: Liapi
authors.forename: J G
authors.initials: JG
authors.lastname: Parnavelas
authors.forename: B
authors.initials: B
authors.lastname: Nadarajah
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D018691:Excitatory Amino Acid Antagonists; D009414:Nerve Growth Factors; D017470:Receptors, Glutamate; D005680:gamma-Aminobutyric Acid; D002118:Calcium