Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9

Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9
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DOI:
10.1126/science.289.5477.313
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发表时间:
2000-07-14
期刊:
影响因子:
56.9
通讯作者:
Blusztajn, JK
Blusztajn, JK
中科院分区:
综合性期刊1区
文献类型:
--
作者:
López-Coviella, I;Berse, B;Blusztajn, JK

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骨形态发生蛋白(BMP)在神经系统发育中具有多种功能。该家族的一个成员BMP-9在胚胎小鼠的隔膜和脊髓中高度表达,表明其可能在调节胆碱能表型中起作用。在培养的神经元中,BMP-9直接诱导编码胆碱乙酰转移酶和囊泡乙酰胆碱转运蛋白的胆碱能基因位点的表达,并上调乙酰胆碱的合成。该作用在BMP-9撤出后逆转。脑室内注射BMP-9增加体内乙酰胆碱水平。尽管某些其他BMP也在体外上调胆碱能表型,但它们不如BMP-9有效。这些数据表明,BMP-9是胆碱能中枢神经系统神经元的分化因子。
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.