Nervous-tissue-specific elimination of microtubule-actin crosslinking factor 1a results in multiple developmental defects in the mouse brain.

Nervous-tissue-specific elimination of microtubule-actin crosslinking factor 1a results in multiple developmental defects in the mouse brain.
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DOI:
10.1016/j.mcn.2010.01.010
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发表时间:
2010-05
影响因子:
3.5
通讯作者:
Liem, Ronald K. H.
Liem, Ronald K. H.
中科院分区:
医学3区
文献类型:
--
作者:
Goryunov, Dmitry;He, Cui-Zhen;Lin, Chyuan-Sheng;Leung, Conrad L.;Liem, Ronald K. H.

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微管-肌动蛋白交联因子1(MACF1)是一种普遍存在的细胞骨架连接蛋白,具有多种剪接异构体,在不同组织中表达。MACF1a亚型含有微管和肌动蛋白结合区,在神经系统中高水平表达。MACF1−/−小鼠是早期胚胎致死的,因此MACF1在神经系统中的作用无法确定。我们特别利用Cre/loxP技术在发育中的小鼠神经系统中敲除了MACF1a。突变小鼠在出生后24-36小时内死于明显的呼吸窘迫。他们的大脑表现为大脑皮质紊乱,混合层结构,海马体锥体层异位,丘脑皮质和皮质分离纤维紊乱,以及再生障碍性前脑和海马区连合。胚胎神经元在穿越皮质板时出现缺陷。我们的数据表明,MACF1在神经元迁移中发挥着关键作用,这取决于它与微丝和微管相互作用的能力。
The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin binding regions and is expressed at high levels in the nervous system. Macf1−/− mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24–36 hrs after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules.
DOI: 10.1083/jcb.149.1.195
发表时间: 2000-04-03
期刊: The Journal of cell biology
影响因子: --
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