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 developin g nervous system. A member of this family, BMP-9, was found to be highly ex pressed in the embryonic mouse septum and spinal cord, indicating a possibl e role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding chol ine acetyltransferase and the vesicular acetylcholine transporter and up-re gulated 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 cholinerg ic phenotype in vitro, they were less effective than BMP-9. These data indi cate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.