抑制因子
生物
皮质脊髓束
大脑皮层
细胞生物学
神经科学
转录因子
生物化学
基因
医学
放射科
磁共振成像
磁共振弥散成像
作者
Wenqi Han,Kenneth Y. Kwan,Sungbo Shim,Mandy M. Lam,Xu Shi,Xuming Xu,Ying Zhu,Mingfeng Li,Nenad Šestan
标识
DOI:10.1073/pnas.1016723108
摘要
The corticospinal (CS) tract is involved in controlling discrete voluntary skilled movements in mammals. The CS tract arises exclusively from layer (L) 5 projection neurons of the cerebral cortex, and its formation requires L5 activity of Fezf2 (Fezl, Zfp312). How this L5-specific pattern of Fezf2 expression and CS axonal connectivity is established with such remarkable fidelity had remained elusive. Here we show that the transcription factor TBR1 directly binds the Fezf2 locus and represses its activity in L6 corticothalamic projection neurons to restrict the origin of the CS tract to L5. In Tbr1 null mutants, CS axons ectopically originate from L6 neurons in a Fezf2-dependent manner. Consistently, misexpression of Tbr1 in L5 CS neurons suppresses Fezf2 expression and effectively abolishes the CS tract. Taken together, our findings show that TBR1 is a direct transcriptional repressor of Fezf2 and a negative regulator of CS tract formation that restricts the laminar origin of CS axons specifically to L5.
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