Plain Language Summary
Preprint version of the study (subsequently published in Nature Neuroscience as PMID 38741020) showing the subcommissural organ secretes thymosin β4, thymosin β10, and NP24 to regulate brain development. SCO-secreted Tβ4 was required for normal brain ventricular development; its reintroduction into SCO-ablated animals substantially rescued developmental defects. First identification of TB4 as an SCO-secreted developmental regulatory peptide.
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. To explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes,,, and, 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.
Authors
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