1. The subcommissural organ regulates brain development via secreted peptides.
- Author
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Zhang T, Ai D, Wei P, Xu Y, Bi Z, Ma F, Li F, Chen XJ, Zhang Z, Zou X, Guo Z, Zhao Y, Li JL, Ye M, Feng Z, Zhang X, Zheng L, Yu J, Li C, Tu T, Zeng H, Lei J, Zhang H, Hong T, Zhang L, Luo B, Li Z, Xing C, Jia C, Li L, Sun W, and Ge WP
- Subjects
- Animals, Mice, Gene Expression Regulation, Developmental, Thymosin metabolism, Thymosin genetics, Mice, Transgenic, Hydrocephalus genetics, Hydrocephalus metabolism, Hydrocephalus pathology, Neurons metabolism, Cell Movement physiology, Peptides metabolism, Mice, Inbred C57BL, Brain metabolism, Brain growth & development, Brain embryology, Subcommissural Organ metabolism
- 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., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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