The subcommissural organ regulates brain development via secreted peptides

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

doi:10.1038/s41593-024-01639-x

The subcommissural organ regulates brain development via secreted peptides

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

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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.

Original language	English (US)
Pages (from-to)	1103-1115
Number of pages	13
Journal	Nature neuroscience
Volume	27
Issue number	6
DOIs	https://doi.org/10.1038/s41593-024-01639-x
State	Published - Jun 2024

ASJC Scopus subject areas

General Neuroscience

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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 & Ge, WP 2024, 'The subcommissural organ regulates brain development via secreted peptides', Nature neuroscience, vol. 27, no. 6, pp. 1103-1115. https://doi.org/10.1038/s41593-024-01639-x

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title = "The subcommissural organ regulates brain development via secreted peptides",

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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",

year = "2024",

month = jun,

doi = "10.1038/s41593-024-01639-x",

language = "English (US)",

volume = "27",

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T1 - The subcommissural organ regulates brain development via secreted peptides

AU - Zhang, Tingting

AU - Ai, Daosheng

AU - Wei, Pingli

AU - Xu, Ying

AU - Bi, Zhanying

AU - Ma, Fengfei

AU - Li, Fengzhi

AU - Chen, Xing Jun

AU - Zhang, Zhaohuan

AU - Zou, Xiaoxiao

AU - Guo, Zongpei

AU - Zhao, Yue

AU - Li, Jun Liszt

AU - Ye, Meng

AU - Feng, Ziyan

AU - Zhang, Xinshuang

AU - Zheng, Lijun

AU - Yu, Jie

AU - Li, Chunli

AU - Tu, Tianqi

AU - Zeng, Hongkui

AU - Lei, Jianfeng

AU - Zhang, Hongqi

AU - Hong, Tao

AU - Zhang, Li

AU - Luo, Benyan

AU - Li, Zhen

AU - Xing, Chao

AU - Jia, Chenxi

AU - Li, Lingjun

AU - Sun, Wenzhi

AU - Ge, Woo Ping

PY - 2024/6

Y1 - 2024/6

N2 - 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.

AB - 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.

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JO - Nature neuroscience

JF - Nature neuroscience

IS - 6

ER -

The subcommissural organ regulates brain development via secreted peptides

Abstract

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