Transcriptional repression by FEZF2 restricts alternative identities of cortical projection neurons.
Transcriptional repression by FEZF2 restricts alternative identities of cortical projection neurons.
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DOI：
10.1016/j.celrep.2021.109269
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发表时间：
2021-06-22
期刊：
影响因子：
8.8
通讯作者：
Chen B
中科院分区：
文献类型：
--
作者：
Tsyporin J;Tastad D;Ma X;Nehme A;Finn T;Huebner L;Liu G;Gallardo D;Makhamreh A;Roberts JM;Katzman S;Sestan N;McConnell SK;Yang Z;Qiu S;Chen B
通过表达泛皮质和亚型特异性效应基因来建立大脑皮层中的投射神经元亚型身份，所述效应基因执行终末分化程序，赋予神经元以神经元能神经元表型和亚型特异性形态、生理和轴突投射。无论是泛皮质的amatergic和亚型特异性的特点是由相同的基因或不同的程序控制仍然在很大程度上是未知的。在这里，我们表明，FEZF 2的功能作为一个转录抑制因子，它调节皮质丘脑和大脑下神经元的亚型特异性的身份，通过选择性抑制基因的表达不适合每个神经元亚型。我们报告说，TLE4，特异性地表达在第6层皮质丘脑神经元，募集FEZF 2抑制第5层大脑下神经元基因。与以前的研究一起，我们的研究结果表明，皮质神经元的身份是由祖细胞中活跃的多个平行通路指定的，而投射神经元亚型特异性身份是通过选择性抑制与分化神经元中的交替身份相关的基因来实现的。第6层皮质丘脑投射神经元和第5层大脑下投射神经元分别将大脑皮质连接到丘脑、脑干和脊髓。Tsyporin等人报道，转录因子FEZF 2通过抑制与交替投射神经元亚型相关的基因的表达来指定这些神经元身份的发展。
Projection neuron subtype identities in the cerebral cortex are established by expressing pan-cortical and subtype-specific effector genes that execute terminal differentiation programs bestowing neurons with a glutamatergic neuron phenotype and subtype-specific morphology, physiology, and axonal projections. Whether pan-cortical glutamatergic and subtype-specific characteristics are regulated by the same genes or controlled by distinct programs remains largely unknown. Here, we show that FEZF2 functions as a transcriptional repressor, and it regulates subtype-specific identities of both corticothalamic and subcerebral neurons by selectively repressing expression of genes inappropriate for each neuronal subtype. We report that TLE4, specifically expressed in layer 6 corticothalamic neurons, is recruited by FEZF2 to inhibit layer 5 subcerebral neuronal genes. Together with previous studies, our results indicate that a cortical glutamatergic identity is specified by multiple parallel pathways active in progenitor cells, whereas projection neuron subtype-specific identity is achieved through selectively repressing genes associated with alternate identities in differentiating neurons. Layer 6 corticothalamic and layer 5 subcerebral projection neurons connect the cerebral cortex to the thalamus and brainstem and spinal cord, respectively. Tsyporin et al. report that the transcription factor FEZF2 specifies the development of these neuronal identities by repressing expression of genes associated with alternate projection neuron subtypes.
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影响因子：
4.6
作者：
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DOI：
10.1073/pnas.0806791105
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2008-10-14
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Guo C;Eckler MJ;McKenna WL;McKinsey GL;Rubenstein JL;Chen B
通讯作者：
Chen B
DOI：
10.1073/pnas.0509032102
发表时间：
2005-12-06
影响因子：
11.1
作者：
Chen, JG;Rasin, MR;Sestan, N
通讯作者：
Sestan, N