The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a
The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a
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DOI：
10.1523/jneurosci.0169-15.2015
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发表时间：
2015-05-13
影响因子：
5.3
通讯作者：
Kukuljan, Manuel
中科院分区：
文献类型：
--
作者：
Canovas, Jose;Andres Berndt, F.;Kukuljan, Manuel
获得不同的神经元命运是大脑皮层功能的基础。我们发现，从第5层神经元在小鼠新皮层的脑下投射的发展依赖于转录因子CTIP 1的高水平表达; CTIP 1与CTIP 2在投射到脑下靶点的神经元中共表达，而与SATB 2在投射到对侧皮层的神经元中共表达。CTIP 1直接抑制第5层的Tbr 1，这似乎是获得大脑下命运的关键步骤。相比之下，第6层中较低水平的CTIP 1是TBR 1表达所必需的，其指导皮质丘脑的命运。CTIP 1似乎并没有发挥关键作用，在收购的胼胝体投影的命运在层5。这些研究结果揭示了一个关键步骤，在收购的细胞命运密切相关的离皮质神经元，并表明，不同剂量的transcription因子是至关重要的，以指定不同的神经元的身份。
The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities.