Department of Psychiatry, POWIC/SANE Research, Oxford University, Warneford Hospital, Oxford OX3 7JX, UK.
Cereb Cortex. 2013 Aug;23(8):1933-41. doi: 10.1093/cercor/bhs181. Epub 2012 Jun 28.
Protocadherins 11X and 11Y are cell adhesion molecules of the δ1-protocadherin family. Pcdh11X is present throughout the mammalian radiation; however, 6 million years ago (MYA), a reduplicative translocation of the Xq21.3 block onto what is now human Yp11 created the Homo sapiens-specific PCDH11Y. Therefore, modern human females express PCDH11X whereas males express both PCDH11X and PCDH11Y. PCDH11X/Y has been subject to accelerated evolution resulting in human-specific changes to both proteins, most notably 2 cysteine substitutions in the PCDH11X ectodomain that may alter binding characteristics. The PCDH11X/Y gene pair is postulated to be critical to aspects of human brain evolution related to the neural correlates of language. Therefore, we raised antibodies to investigate the temporal and spatial expression of PCDH11X/Y in cortical and sub-cortical areas of the human fetal brain between 12 and 34 postconceptional weeks. We then used the antibodies to determine if this expression was consistent in a series of adult brains. PCDH11X/Y immunoreactivity was detectable at all developmental stages. Strong expression was detected in the fetal neocortex, ganglionic eminences, cerebellum, and inferior olive. In the adult brain, the cerebral cortex, hippocampal formation, and cerebellum were strongly immunoreactive, with expression also detectable in the brainstem.
原钙黏蛋白 11X 和 11Y 是 δ1-原钙黏蛋白家族的细胞黏附分子。Pcdh11X 存在于整个哺乳动物辐射中；然而，600 万年前（MYA），Xq21.3 块的重复易位到现在的人类 Yp11 上，创造了智人特异性的 PCDH11Y。因此，现代女性表达 PCDH11X，而男性则表达 PCDH11X 和 PCDH11Y。PCDH11X/Y 经历了加速进化，导致两种蛋白质都发生了人类特有的变化，最显著的是 PCDH11X 胞外域的 2 个半胱氨酸取代，这可能改变了结合特性。PCDH11X/Y 基因对与语言神经相关的人类大脑进化的某些方面具有重要意义。因此，我们制备了抗体来研究 PCDH11X/Y 在人类胎儿大脑皮质和皮质下区域的时空表达，从受精后 12 周到 34 周。然后，我们使用这些抗体来确定这种表达在一系列成人脑中是否一致。PCDH11X/Y 免疫反应性在所有发育阶段都可检测到。在胎儿新皮质、神经节隆起、小脑和下橄榄中检测到强烈的表达。在成人脑中，大脑皮质、海马结构和小脑强烈免疫反应性，在脑干中也可检测到表达。
