Johnson Matthew B, Kawasawa Yuka Imamura, Mason Christopher E, Krsnik Zeljka, Coppola Giovanni, Bogdanović Darko, Geschwind Daniel H, Mane Shrikant M, State Matthew W, Sestan Nenad
Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
Neuron. 2009 May 28;62(4):494-509. doi: 10.1016/j.neuron.2009.03.027.
Our understanding of the evolution, formation, and pathological disruption of human brain circuits is impeded by a lack of comprehensive data on the developing brain transcriptome. A whole-genome, exon-level expression analysis of 13 regions from left and right sides of the mid-fetal human brain revealed that 76% of genes are expressed, and 44% of these are differentially regulated. These data reveal a large number of specific gene expression and alternative splicing patterns, as well as coexpression networks, associated with distinct regions and neurodevelopmental processes. Of particular relevance to cognitive specializations, we have characterized the transcriptional landscapes of prefrontal cortex and perisylvian speech and language areas, which exhibit a population-level global expression symmetry. We show that differentially expressed genes are more frequently associated with human-specific evolution of putative cis-regulatory elements. These data provide a wealth of biological insights into the complex transcriptional and molecular underpinnings of human brain development and evolution.
由于缺乏关于发育中大脑转录组的全面数据，我们对人类脑回路的进化、形成和病理破坏的理解受到阻碍。对胎儿中期人脑左右两侧13个区域进行的全基因组外显子水平表达分析表明，76%的基因有表达，其中44%受到差异调节。这些数据揭示了大量与不同区域和神经发育过程相关的特定基因表达和可变剪接模式，以及共表达网络。与认知特化特别相关的是，我们已经描绘了前额叶皮层以及颞周言语和语言区域的转录图谱，这些区域表现出群体水平的整体表达对称性。我们表明，差异表达基因更频繁地与假定顺式调控元件的人类特异性进化相关。这些数据为人类大脑发育和进化的复杂转录和分子基础提供了丰富的生物学见解。
