Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9.
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.
López-Coviella
I
I
Department of Psychiatry and Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Berse
B
B
Krauss
R
R
Thies
R S
RS
Blusztajn
J K
JK
D000109:Acetylcholine / Q000096:biosynthesis; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System; D002795:Choline O-Acetyltransferase / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D055427:Growth Differentiation Factor 2; D026901:Membrane Transport Proteins; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020665:Septum of Brain / Q000196:embryology / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D015854:Up-Regulation; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D016222:Fibroblast Growth Factor 2; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine