The hallmarks of FOXG1 syndrome, which results from mutations in a single FOXG1 allele, include cortical atrophy and corpus callosum agenesis. However, the etiology for these structural deficits and the role of FOXG1 in cortical projection neurons remain unclear. Here we demonstrate that Foxg1 in pyramidal neurons plays essential roles in establishing cortical layers and the identity and axon trajectory of callosal projection neurons. The neuron-specific actions of Foxg1 are achieved by forming a transcription complex with Rp58. The Foxg1-Rp58 complex directly binds and represses Robo1, Slit3, and Reelin genes, the key regulators of callosal axon guidance and neuronal migration. We also found that inactivation of one Foxg1 allele specifically in cortical neurons was sufficient to cause cerebral cortical hypoplasia and corpus callosum agenesis. Together, this study reveals a novel gene regulatory pathway that specifies neuronal characteristics during cerebral cortex development and sheds light on the etiology of FOXG1 syndrome. VIDEO ABSTRACT.

中文翻译：

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FOXG1协调新皮质组织和皮质-皮质连接。

由单个FOXG1等位基因突变产生的FOXG1综合征的标志包括皮质萎缩和体发育不全。但是，这些结构缺陷的病因学和FOXG1在皮层投射神经元中的作用仍不清楚。在这里，我们证明，锥体神经元中的Foxg1在建立皮质层以及call投射神经元的身份和轴突轨迹中起着至关重要的作用。Foxg1的神经元特异性作用是通过与Rp58形成转录复合物来实现的。Foxg1-Rp58复合体直接结合并抑制Robo1，Slit3和Reelin基因，后者是call轴突引导和神经元迁移的关键调节因子。我们还发现，一个Foxg1等位基因在皮层神经元中的失活足以引起大脑皮层发育不全和体发育不全。总之，这项研究揭示了一种新的基因调控途径，该途径可调节大脑皮层发育过程中的神经元特征，并阐明FOXG1综合征的病因。视频摘要。