大脑皮质含有百余种不同类型的神经元，这些神经元形态、轴突投射和功能各不相同。不同亚型神经元的特化是神经环路形成的基础，但是目前关于亚型特化调控的认识还十分有限。我们前期研究发现在有丝分裂后神经元中条件性敲除Foxg1导致皮层深层的胼胝体投射神经元、皮质丘脑投射神经元以及皮质脊髓/脑干投射神经元亚型特化异常。本项目将利用CAG-CreERTM、Nestin-CreERTM以及Nex-Cre条件性敲除 Foxg1，明确Foxg1对深层投射神经元亚型特化的影响。通过CHIP检测不同特化时间节点Foxg1是否对亚型决定因子Fezf2, Ctip2, Satb2，Tbr1的表达具有直接的调控，抑或在上游通过Sox家族对其进行调控，在此基础上阐明FoxG1对亚型决定因子时空上有序表达的精确调控，揭示特化机制。本研究有助于深入理解神经元亚型特化的调控及Foxg1突变患者认知和运动功能障碍的发病机制。

The mammalian cortex consists of hundreds of neuronal subtypes that exhibit distinct morphologies, process projections and specific functions. The precise specification of cortical subtype projection neurons is the basis of cortical neural circuit formation. Currently, the mechanism of subtype specification still remain unclear. Previously we have found that the transcription factor Foxg1 is critical for the post-mitotic subtype specification of deeper cortical neurons including callosal projection neurons, corticothalamical projection neurons and subcerebral projection neurons. Conditional deletion of foxg1 leads to severe specification defects on these subtypes. In this study, by spatiotemporal disruption of Foxg1 achieved by crossing foxg1fl/fl line with CAG-CreERTM, Nestin-CreERTM or Nex-Cre respectively, we will explore the role of Foxg1 in the subtype specification of deeper cortical neurons, and to elucidate the mechanism of Foxg1 controlling subtype specification. Using CHIP to examine whether Foxg1 directly regulates the expression of the key determinant genes including Fezf2, Ctip2, Satb2, Tbr1 or through their upstream Sox genes. Our study will provide insights into the mechanisms of subtype specification of cortical neurons and the pathology of FoxG1-related disorders.