Acetylcholinesterase is required for neuronal and muscular development in the zebrafish embryo
Acetylcholinesterase is required for neuronal and muscular development in the zebrafish embryo
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DOI：
10.1038/nn788
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发表时间：
2002-02-01
影响因子：
25
通讯作者：
Strähle, U
中科院分区：
文献类型：
--
作者：
Behra, M;Cousin, X;Strähle, U
神经递质乙酰胆碱（ACh）在胆碱能系统的中枢和神经肌肉突触中具有至关重要的作用。在释放到突触间隙后，ACh被乙酰胆碱酯酶（AChE）迅速降解。我们已经确定了一个突变的斑马鱼，这完全废除ACh水解纯合子动物的AchE基因。胚胎最初是能动的，但随后发展为瘫痪。突变胚胎在肌纤维形成和神经支配方面表现出缺陷，初级感觉神经元过早死亡。乙酰胆碱受体α亚基的纯合性功能丧失等位基因抑制了疼痛突变体的神经肌肉表型，表明神经肌肉发育障碍是由突变体中乙酰胆碱受体的激活介导的。在这里，我们提供了遗传证据的非经典功能的乙酰胆碱酯酶在脊椎动物的发展。
The neurotransmitter acetylcholine (ACh) has a crucial role in central and neuromuscular synapses of the cholinergic system. After release into the synaptic cleft, ACh is rapidly degraded by acetylcholinesterase (AChE). We have identified a mutation in the ache gene of the zebrafish, which abolishes ACh hydrolysis in homozygous animals completely. Embryos are initially motile but subsequently develop paralysis. Mutant embryos show defects in muscle fiber formation and innervation, and primary sensory neurons die prematurely. The neuromuscular phenotype in ache mutants is suppressed by a homozygous loss-of-function allele of the alpha-subunit of the nicotinic acetylcholine receptor (nAChR), indicating that the impairment of neuromuscular development is mediated by activation of nAChR in the mutant. Here we provide genetic evidence for non-classical functions of AChE in vertebrate development.