Comparison of munc-18 and cdk5 expression in the nervous system during mouse embryogenesis

Comparison of munc-18 and cdk5 expression in the nervous system during mouse embryogenesis
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DOI:
10.1016/s0306-4522(99)00372-3
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发表时间:
1999-01-01
期刊:
影响因子:
3.3
通讯作者:
Morgan, JI
Morgan, JI
中科院分区:
医学3区
文献类型:
--
作者:
Han, SH;Morgan, JI

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细胞周期蛋白依赖性激酶5(Cdk 5)及其神经元特异性激活剂p35对神经元的正常迁移至关重要。虽然p35基因缺失小鼠的缺陷主要局限于大脑皮层,但cdk 5基因缺失小鼠的异常在海马和小脑也很明显。这表明,额外的细胞周期蛋白样激活剂,如Munc-18,必须与CdkS在一些迁移神经元共表达。因此,通过原位杂交确定了munc-18和cdk 5在发育中的小鼠神经系统中的表达模式。在胚胎11.5-13.5天发育的新皮质中,cdk 5在增殖区以及迁移和有丝分裂后的神经元中表达。与此相反,munc-18信使RNA仅在迁移后,分化的神经元中检测到。在小脑和海马中,cdk 5在增殖、迁移和迁移后神经元中表达,而munc-18在迁移和迁移后神经元中表达,这支持了munc-18可以补偿海马和小脑中迁移神经元中p35的缺失,而不能补偿大脑皮层中p35的缺失的假说。Munc-18水平在胚胎发生晚期和成年期大幅增加。因此,Munc-18的功能最可能与成熟神经元相关,并且在迁移中与p35的任何冗余可能是偶然的。(C)1999年IBRO。出版社:Elsevier Science Ltd
Cyclin-dependent kinase-5 (Cdk5) and its neuron-specific activator, p35, are essential for the proper migration of neurons. While the defects in p35 null mice are largely confined to the cerebral cortex, the anomalies in cdk5 nullizygous mice are also evident in the hippocampus and cerebellum. This suggested that additional cyclin-like activators, such as Munc-18, must be coexpressed with CdkS in some migrating neurons. Therefore, the expression patterns of munc-18 and cdk5 were determined in the developing mouse nervous system by in situ hybridization. In the embryonic day 11.5-13.5 developing neocortex, cdk5 was expressed in the proliferative zone and also in migratory and postmitotic neurons. In contrast, munc-18 messenger RNA was only detected in postmigratory, differentiated neurons. In the cerebellum and the hippocampus, cdk5 was expressed in proliferative, migrating and postmigratory neurons, while munc-18 was expressed in migrating and postmigratory neurons.This supports the hypothesis that Munc-18 could compensate for the loss of p35 in migrating neurons in the hippocampus and cerebellum, but not the cerebral cortex. Munc-18 levels increased substantially during late embryogenesis and into adulthood. Therefore, the function of Munc-18 is most likely relevant to mature neurons and any redundancy with p35 in migration is probably fortuitous. (C) 1999 IBRO. Published by Elsevier Science Ltd.