Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia
Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia
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DOI：
10.1016/s0896-6273(00)80651-0
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发表时间：
1998-12-01
期刊：
影响因子：
16.2
通讯作者：
Walsh, CA
中科院分区：
文献类型：
--
作者：
Fox, JW;Lamperti, ED;Walsh, CA
远距离定向迁移在大脑皮层中尤为显著，在大脑深处产生的有丝分裂后神经元迁移形成具有不同形式和功能的层。在x连锁的显性人类疾病脑室周围异位（PH）中，许多神经元不能迁移，并以结节的形式存在于脑室表面。患有PH的雌性存在癫痫和其他体征，包括动脉导管未闭和凝血功能障碍，而半合子雄性在胚胎期死亡。我们已经确定PH基因为丝蛋白I (FLN1)，它编码一种肌动蛋白交联磷酸化蛋白，将配体-受体结合转化为肌动蛋白重组，这是许多细胞类型运动所必需的。FLN1在发育中的皮层中显示出先前未被识别的高水平表达，是神经元向皮层迁移所必需的，也是胚胎发生所必需的。
Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin I (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis.