Cytoskeleton in action: lissencephaly, a neuronal migration disorder.
Cytoskeleton in action: lissencephaly, a neuronal migration disorder.
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DOI：
10.1002/wdev.67
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发表时间：
2013-03
影响因子：
--
通讯作者：
Wynshaw-Boris, Anthony
中科院分区：
文献类型：
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作者：
Moon, Hyang Mi;Wynshaw-Boris, Anthony
在新皮层发育期间，神经元从其出生地到其最终位置的广泛迁移运动对于突触回路的协调布线和适当的神经功能是必不可少的。神经元迁移的失败或延迟会导致皮质分层的严重异常，从而导致人类无脑回畸形（“平滑脑”），一种神经元迁移障碍。无脑回畸形患者的大脑皮层中有较少的回旋回，神经元的皮层层受损。由于微管和肌动蛋白相关蛋白在调节神经元迁移过程中微管和肌动蛋白细胞骨架的动力学中起着重要的作用，参与细胞骨架过程的关键基因的基因突变或缺失导致人类无脑畸形和小鼠神经元迁移缺陷。在神经元迁移过程中，微管组织和运输由PAFAH 1B 1（LIS 1），DCX，YWHAE和微管蛋白控制。肌动蛋白应力纤维由PAFAH 1B 1（LIS 1）、DCX、CANN和VLDLR/LRP 8（APOER 2）调节。这两种细胞骨架系统之间存在几个重要水平的串扰，以在发育中建立准确的皮质图案。最近的理解，通过调节细胞骨架动力学，从人类和小鼠的遗传学以及分子和细胞分析，管理神经元迁移的蛋白质网络，提供了新的见解神经元迁移障碍，并可能帮助我们设计新的治疗策略，这样的脑畸形。
During neocortical development, the extensive migratory movements of neurons from their place of birth to their final location are essential for the coordinated wiring of synaptic circuits and proper neurological function. Failure or delay in neuronal migration causes severe abnormalities in cortical layering, which consequently results in human lissencephaly (‘smooth brain’), a neuronal migration disorder. The brains of lissencephaly patients have less-convoluted gyri in the cerebral cortex with impaired cortical lamination of neurons. Since microtubule- and actin-associated proteins play important functions in regulating the dynamics of microtubule and actin cytoskeletons during neuronal migration, genetic mutations or deletions of crucial genes involved in cytoskeletal processes lead to lissencephaly in human and neuronal migration defects in mouse. During neuronal migration, microtubule organization and transport are controlled by PAFAH1B1 (LIS1), DCX, YWHAE, and tubulin. Actin stress fibers are modulated by PAFAH1B1 (LIS1), DCX, RELN, and VLDLR/LRP8 (APOER2). There are several important levels of crosstalk between these two cytoskeletal systems to establish accurate cortical patterning in development. The recent understanding of the protein networks that govern neuronal migration by regulating cytoskeletal dynamics, from human and mouse genetics as well as molecular and cellular analyses, provides new insights on neuronal migration disorders and may help us devise novel therapeutic strategies for such brain malformations.