Subcommissural organ (SCO) contributes to brain development via SCO-secreted peptides
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Chenxi Jia
PROVIDER: PXD040641 | iProX | Tue Feb 04 00:00:00 GMT 2025
REPOSITORIES: iProX
Publications
The subcommissural organ regulates brain development via secreted peptides.
Zhang Tingting T Ai Daosheng D Wei Pingli P Xu Ying Y Bi Zhanying Z Ma Fengfei F Li Fengzhi F Chen Xing-Jun XJ Zhang Zhaohuan Z Zou Xiaoxiao X Guo Zongpei Z Zhao Yue Y Li Jun-Liszt JL Ye Meng M Feng Ziyan Z Zhang Xinshuang X Zheng Lijun L Yu Jie J Li Chunli C Tu Tianqi T Zeng Hongkui H Lei Jianfeng J Zhang Hongqi H Hong Tao T Zhang Li L Luo Benyan B Li Zhen Z Xing Chao C Jia Chenxi C Li Lingjun L Sun Wenzhi W Ge Woo-Ping WP
Nature neuroscience 20240513 6
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 gen ...[more]
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Project description:To explore the role of SCO and its functional mechanism, we performed RNAseq between SCO and hippocampus at different stage to identify the expression of some unique genes and possible pathway related to the function of SCO. We cofirmed the role of SCO in neuronal development and identified three SCO-derived peptides which can contributed to neurite development and neuronal survival .
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Project description: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, 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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Project description:Subcommissural organ (SCO) contributes to brain development via SCO-secreted peptides
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Project description:Subcommissural organ (SCO) contributes to brain development via SCO-secreted peptides.
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Project description:Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance via inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy via effects on muscle protein turnover. To investigate this, eight-week-old male C57BL/6J mice were fed a chow (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce hepatic steatosis, after which the livers were excised and cut into ~200 µm slices. Slices were cultured to collect secretion products (conditioned medium; CM). Differentiated L6-GLUT4myc myotubes were incubated with chow or HFD CM to measure glucose uptake. Differentiated C2C12 myotubes were incubated with chow or HFD CM to measure protein synthesis and breakdown, and gene expression via RNA sequencing. Furthermore, proteomics analysis was performed in chow and HFD CM. It was found that HFD CM caused insulin resistance in L6-GLUT4myc myotubes compared with chow CM, as indicated by a blunted insulin-stimulated increase in glucose uptake. Furthermore, protein breakdown was increased in C2C12 cells incubated with HFD CM, while there was no effect on protein synthesis. RNA profiling of C2C12 cells indicated that 197 genes were differentially expressed after incubation with HFD CM, compared with chow CM, and pathway analysis showed that pathways related to anatomical structure and function were enriched. Proteomic analysis of the CM showed that 32 proteins were differentially expressed in HFD CM compared with chow CM. Pathway enrichment analysis indicated that these proteins had important functions with respect to insulin-like Growth Factor transport and uptake, and affect post-translational processes, including protein folding, protein secretion and protein phosphorylation. In conclusion, the results of this study support the hypothesis that secretion products from the liver contribute to the development of muscle atrophy in individuals with hepatic steatosis.
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