title: Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins.
abstract: In the present study, we examined whether the bone morphogenetic proteins (BMPs), which are important in the developmental specification of transmitter type in certain classes of neurons, might also play a role in signaling the differentiation of a dopaminergic (DA) phenotype. We found that BMP-2, -4 and -6 were each capable of inducing, in a dose and time dependent manner, moderate levels of the DA enzyme tyrosine hydroxylase (TH) in cultured neurons from the mouse embryonic striatum. In contradistinction to other TH-inducing agents, BMPs initiated de novo TH expression without the required synergy of exogenous growth factors or co-activating substances and in neurons presumably aged (E16) beyond the critical period for induction. However, the appearance of TH in induced cells was short-lived (24 h) and could not be prolonged by repeated supplementation with the BMPs. Inhibitors of the mitogen-activated protein kinase (MAPK/ERK) signaling pathway, PD98059 and apigenin, did not prevent TH induction by BMP-4, as they did other TH inducing agents, indicating that the MAPK/ERK pathway does not mediate BMPs effects on TH expression. We conclude that BMP-2, -4 and -6 can be added to the expanding inventory of agents capable of inducing TH, making them potentially important in the specification of a DA phenotype in stem/precursor cells for the treatment of Parkinson's disease.
authors.affiliation: Department of Neurology, Thomas Jefferson University Medical College, 1025 Walnut Street, Philadelphia, PA 19107, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Stull
authors.forename: J W
authors.initials: JW
authors.lastname: Jung
authors.forename: L
authors.initials: L
authors.lastname: Iacovitti
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000166:cytology; D005419:Flavonoids / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D010641:Phenotype; D011247:Pregnancy; D016212:Transforming Growth Factor beta; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis*
chemical_list: C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C525817:Bmp6 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016212:Transforming Growth Factor beta; D014446:Tyrosine 3-Monooxygenase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004298:Dopamine