近日，瑞士日内瓦大学教授Esther Klingler及其小组的研究发现驱动物种特异性皮质特征的发育基因表达模式。相关论文于2026年5月13日发表于国际顶尖学术期刊《自然》杂志上。

为了研究这种可能性，该课题组人员利用机器视觉来识别和比较发育中的小鼠和人类新皮层以及人类皮质类器官中细胞类型特异性基因表达模式。利用这种方法，该团队鉴定了具有进化保守或分化转录调控的基因，揭示了物种特异性细胞-时间基因表达模式。在这些基因中，转录因子基因JUNB在人类祖细胞和同母细胞神经元中表现出互斥表达。

通过在小鼠和人类皮质类器官中进行的细胞类型特异性功能增益和功能丧失实验，研究组发现JUNB双向控制人类皮质特征，包括祖细胞增殖率、神经元产生时间和总神经元输出。该课题组人员发现IRF1是一种人类放射状胶质细胞特异性调节剂，当它在无主题放射状胶质细胞中表达时，激活JUNB并招募人类样基因调控网络，证明了平衡发育程序的跨物种激活。总之，这些发现揭示了共享基因的细胞-时间调控如何驱动物种特异性皮质特征，并为理解和操纵这些进化程序提供了分子框架。

据悉，大脑皮层在大小和组织上显示出物种特有的差异，这可能解释了不同的行为能力。这些结构差异可能反映了共享基因发育表达的进化变化。

附：英文原文

Title: Developmental gene expression patterns driving species-specific cortical features

Author: Javed, Awais, Gmez, Luca, Pravata, Veronica, Sarhadi, Moein, Giudice, Quentin Lo, Szalai, Tima, Aubert, La, Ribierre, Tho, Nguyen, Laurent, Cappello, Silvia, Jabaudon, Denis, Klingler, Esther

Issue&Volume: 2026-05-13

Abstract: The cerebral cortex shows species-specific variations in size and organization, which probably account for distinct behavioural abilities1. These structural differences may reflect evolutionary changes in the developmental expression of shared genes. Here, to investigate this possibility, we used machine vision to identify and compare cell-type-specific gene expression patterns in the developing mouse and human neocortex, and in human cortical organoids. Using this approach, we identified genes with evolutionarily conserved or divergent transcriptional regulation, revealing species-specific cyto-temporal gene expression patterns. Among such genes, the transcription factor gene JUNB showed mutually exclusive expression in human progenitors and mouse neurons. Through cell-type-specific gain- and loss-of-function experiments in mice and human cortical organoids, we show that JUNB bidirectionally controls human cortical features, including progenitor proliferation rates, neuronal production timing and total neuronal output. We identify IRF1 as a human radial glia-specific regulator that, when expressed in mouse radial glia, activates JUNB and recruits human-like gene regulatory networks, demonstrating cross-species activation of poised developmental programmes. Together, these findings reveal how cyto-temporal regulation of shared genes drives species-specific cortical features, and provide a molecular framework for understanding and manipulating these evolutionary programmes.

DOI: 10.1038/s41586-026-10491-x

Source: https://www.nature.com/articles/s41586-026-10491-x