Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA.
Cell Rep. 2021 Jun 22;35(12):109269. doi: 10.1016/j.celrep.2021.109269.
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.
大脑皮层中的投射神经元亚型身份是通过表达广泛表达的皮层和亚型特异性效应基因来建立的,这些基因执行终末分化程序,赋予神经元谷氨酸能神经元表型和亚型特异性形态、生理学和轴突投射。广泛表达的皮层谷氨酸能和亚型特异性特征是否由相同的基因调控,或者由不同的程序控制,在很大程度上仍然未知。在这里,我们表明 FEZF2 作为转录抑制剂发挥作用,通过选择性地抑制每个神经元亚型不适当的基因表达,来调节皮质丘脑和皮质下神经元的亚型特异性身份。我们报告说,TLE4 特异性表达在 6 层皮质丘脑神经元中,它被 FEZF2 募集来抑制 5 层皮质下神经元基因。结合以前的研究,我们的结果表明,皮层谷氨酸能身份是由祖细胞中多个平行途径特异性指定的,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替代身份相关的基因来实现的。