Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), 03550 Sant Joan d'Alacant, Spain.
Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal.
Cereb Cortex. 2017 Nov 1;27(11):5054-5069. doi: 10.1093/cercor/bhw290.
The thalamus is a central brain structure with topographically ordered long-range axonal projections that convey sensory information to the cortex via distinct nuclei. Although there is an increasing knowledge about genes important for thalamocortical (TC) development, the identification of genetic landmarks of the distinct thalamic nuclei during the embryonic development has not been addressed systematically. Indeed, a more comprehensive understanding of how the axons from the individual nuclei find their way and connect to their corresponding cortical area is called for. Here, we used a genetic dual labeling strategy in mice to purify distinct principal sensory thalamic neurons. Subsequent genome-wide transcriptome profiling revealed genes specifically expressed in each nucleus during embryonic development. Analysis of regulatory regions of the identified genes revealed key transcription factors and networks that likely underlie the specification of individual sensory-modality TC connections. Finally, the importance of correct axon targeting for the specific sensory-modality population transcriptome was evidenced in a Sema6A mutant, in which visual TC axons are derailed at embryonic life. In sum, our data determined the developmental transcriptional profile of the TC neurons that will eventually support sensory processing.
丘脑是大脑的一个中枢结构,具有拓扑有序的长程轴突投射,通过不同的核将感觉信息传递到皮层。尽管人们对丘脑皮质(TC)发育重要的基因有了越来越多的了解,但在胚胎发育过程中,特定丘脑核的遗传标志物的确定尚未得到系统解决。事实上,人们需要更全面地了解来自各个核的轴突如何找到自己的路并连接到相应的皮层区域。在这里,我们使用了一种在小鼠中的遗传双重标记策略来纯化不同的主要感觉丘脑神经元。随后的全基因组转录组谱分析显示了在胚胎发育过程中每个核特异性表达的基因。对鉴定基因的调控区分析揭示了可能是特定感觉模态 TC 连接特异性的关键转录因子和网络。最后,在 Sema6A 突变体中证明了正确的轴突靶向对于特定感觉模态群体转录组的重要性,在该突变体中,视觉 TC 轴突在胚胎期发生偏离。总之,我们的数据确定了最终支持感觉处理的 TC 神经元的发育转录谱。