INDUCTION OF MIDBRAIN DOPAMINERGIC-NEURONS BY SONIC HEDGEHOG
INDUCTION OF MIDBRAIN DOPAMINERGIC-NEURONS BY SONIC HEDGEHOG
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DOI：
10.1016/0896-6273(95)90062-4
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发表时间：
1995-07-01
期刊：
影响因子：
16.2
通讯作者：
ROSENTHAL, A
中科院分区：
文献类型：
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作者：
HYNES, M;PORTER, JA;ROSENTHAL, A
中脑多巴胺能神经元，其损失在成年人中的结果，帕金森氏病，可以指定在胚胎发育过程中的接触依赖性信号从底板细胞。在这里，我们表明，氨基末端产物的Sonic刺猬自蛋白水解（SHH-N），地板细胞表达的诱导信号，可以诱导多巴胺能神经元在体外。我们进一步表明，操纵，以增加环AMP依赖性蛋白激酶A，这是已知的拮抗刺猬信号的活性，可以阻止多巴胺能神经元诱导底板细胞。我们的研究结果和其他研究表明，SHH-N可以剂量依赖的方式诱导神经管内不同类型的细胞。我们的研究结果也为帕金森病的潜在细胞移植治疗提供了基础。
Midbrain dopaminergic neurons, whose loss in adults results in Parkinson's disease, can be specified during embryonic development by a contact-dependent signal from floor plate cells. Here we show that the aminoterminal product of Sonic hedgehog autoproteolysis (SHH-N), an inductive signal expressed by floor plate cells, can induce dopaminergic neurons in vitro. We show further that manipulations to increase the activity of cyclic AMP-dependent protein kinase A, which is known to antagonize hedgehog signaling, can block dopaminergic neuron induction by floor plate cells. Our results and those of other studies indicate that SHH-N can function in a dose-dependent manner to induce different cell types within the neural tube. Our results also provide the basis for a potential cell transplantation therapy for Parkinson's disease.