Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency
Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency
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DOI：
10.1073/pnas.0908790107
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发表时间：
2010-03-16
影响因子：
11.1
通讯作者：
Young, Stephen G.
中科院分区：
文献类型：
--
作者：
Coffinier, Catherine;Chang, Sandy Y.;Young, Stephen G.
核层是核层的组成部分，核层是细胞核的结构支架。层蛋白A和C的缺陷会导致一系列人类疾病，包括肌肉营养不良、脂肪营养不良和早衰症，但没有任何疾病与层蛋白B1或B2的丢失有关。为了探索lamin B2的功能相关性，我们产生了lamin B2缺陷的小鼠，发现它们有严重的类似于无脑的脑异常，大脑皮层和小脑中神经元的异常分层。这种神经元分层的异常是由于有缺陷的神经元迁移，这一过程依赖于细胞核在细胞内的有组织的运动。这些研究确立了层蛋白B2在神经元迁移和脑发育中的重要作用。
Nuclear lamins are components of the nuclear lamina, a structural scaffolding for the cell nucleus. Defects in lamins A and C cause an array of human diseases, including muscular dystrophy, lipodystrophy, and progeria, but no diseases have been linked to the loss of lamins B1 or B2. To explore the functional relevance of lamin B2, we generated lamin B2-deficient mice and found that they have severe brain abnormalities resembling lissencephaly, with abnormal layering of neurons in the cerebral cortex and cerebellum. This neuronal layering abnormality is due to defective neuronal migration, a process that is dependent on the organized movement of the nucleus within the cell. These studies establish an essential function for lamin B2 in neuronal migration and brain development.