Fezl is required for the birth and specification of corticospinal motor neurons
Fezl is required for the birth and specification of corticospinal motor neurons
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DOI：
10.1016/j.neuron.2005.08.030
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发表时间：
2005-09-15
期刊：
影响因子：
16.2
通讯作者：
Macklis, JD
中科院分区：
文献类型：
--
作者：
Molyneaux, BJ;Arlotta, P;Macklis, JD
在新皮质发育过程中，控制神经前体细胞分化为不同亚型神经元的分子机制尚不清楚。在这里，我们报告了FEZL对于皮质脊髓运动神经元和其他大脑下投射神经元的规范是必需的，这些神经元在FEZL缺失突变的新皮质中缺失。FEZL(-/-)皮层的细胞死亡没有增加，迁移也没有异常，这表明大脑下投射神经元的缺失是由于命运指定的失败。与之形成鲜明对比的是，在同一层和其他皮质中的其他神经元群体是正常出生的。FEZL的过度表达导致了大脑下投射神经元的过度产生，并阻止了这些神经元在生发区的迁移。这些数据表明，FEZL在皮质脊髓运动神经元和其他大脑下投射神经元的指定中起着核心作用，控制着关于谱系特异性与神经前体细胞分化的早期决定。
The molecular mechanisms controlling the differentiation of neural progenitors into distinct subtypes of neurons during neocortical development are unknown. Here, we report that Fezl is required for the specification of corticospinal motor neurons and other subcerebral projection neurons, which are absent from Fezl null mutant neocortex. There is neither an increase in cell death in Fezl(-/-) cortex nor abnormalities in migration, indicating that the absence of subcerebral projection neurons is due to a failure in fate specification. In striking contrast, other neuronal populations in the same and other cortical layers are born normally. Overexpression of Fezl results in excess production of subcerebral projection neurons and arrested migration of these neurons in the germinal zone. These data indicate that Fezl plays a central role in the specification of corticospinal motor neurons and other subcerebral projection neurons, controlling early decisions regarding lineage-specific differentiation from neural progenitors.