Abstract
Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / biosynthesis
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Animals
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Bone Morphogenetic Proteins / physiology*
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Carrier Proteins / genetics
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Cells, Cultured
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Central Nervous System
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Choline O-Acetyltransferase / genetics
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Embryo, Mammalian / metabolism
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Fibroblast Growth Factor 2 / physiology
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Gene Expression Regulation, Developmental
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Gene Expression Regulation, Enzymologic
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Growth Differentiation Factor 2
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Membrane Transport Proteins*
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Mice
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Neurons / metabolism
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Phenotype
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RNA, Messenger / metabolism
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Septum of Brain / embryology
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Septum of Brain / metabolism
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Spinal Cord / embryology
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Spinal Cord / metabolism
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Up-Regulation
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Vesicular Acetylcholine Transport Proteins
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Vesicular Transport Proteins*
Substances
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Bone Morphogenetic Proteins
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Carrier Proteins
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Gdf2 protein, mouse
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Growth Differentiation Factor 2
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Membrane Transport Proteins
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RNA, Messenger
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Slc18a3 protein, mouse
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Vesicular Acetylcholine Transport Proteins
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Vesicular Transport Proteins
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Fibroblast Growth Factor 2
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Choline O-Acetyltransferase
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Acetylcholine