近日，中国脑研究所戈鹉平团队研究显示，下连合器通过分泌多肽调节大脑发育。2024年5月13日，国际知名学术期刊《自然—神经科学》发表了这一成果。

研究人员表示，下连合器(SCO)是位于脑脊液导水管入口处的腺体。它存在于像文昌鱼和人类这样的远亲物种中，但它的功能在很大程度上是未知的。

为了探索下连合器（SCO）功能，该课题组人员比较了SCO和非SCO脑区的转录组，发现了三个基因Sspo、Car3和Spdef在SCO中高表达。从内源性启动子/增强子元件中表达Cre重组酶的小鼠，在胚胎发育期间被定向到基因上吞噬SCO细胞，导致严重的脑积水和神经元迁移以及神经元轴突和树突发育缺陷。

无偏差肽组学分析显示，三种由SCO衍生的肽，即胸腺肽β4、胸腺肽β10和NP24富集，并将它们重新引入SCO缺失的脑室，大大挽救了发育缺陷。总之，这些数据确定了SCO在大脑发育中的关键作用。

附：英文原文

Title: The subcommissural organ regulates brain development via secreted peptides

Author: Zhang, Tingting, Ai, Daosheng, Wei, Pingli, Xu, Ying, Bi, Zhanying, Ma, Fengfei, Li, Fengzhi, Chen, Xing-jun, Zhang, Zhaohuan, Zou, Xiaoxiao, Guo, Zongpei, Zhao, Yue, Li, Jun-Liszt, Ye, Meng, Feng, Ziyan, Zhang, Xinshuang, Zheng, Lijun, Yu, Jie, Li, Chunli, Tu, Tianqi, Zeng, Hongkui, Lei, Jianfeng, Zhang, Hongqi, Hong, Tao, Zhang, Li, Luo, Benyan, Li, Zhen, Xing, Chao, Jia, Chenxi, Li, Lingjun, Sun, Wenzhi, Ge, Woo-ping

Issue&Volume: 2024-05-13

Abstract: The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

DOI: 10.1038/s41593-024-01639-x

Source: https://www.nature.com/articles/s41593-024-01639-x