Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development

IF 21.2 1区医学 Q1 NEUROSCIENCES

Nature neuroscience Pub Date : 2025-05-28 DOI:10.1038/s41593-025-01972-9

Ya’el Courtney, Joshua P. Head, Neil Dani, Olga V. Chechneva, Frederick B. Shipley, Yong Zhang, Michael J. Holtzman, Cameron Sadegh, Towia A. Libermann, Maria K. Lehtinen

{"title":"Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development","authors":"Ya’el Courtney, Joshua P. Head, Neil Dani, Olga V. Chechneva, Frederick B. Shipley, Yong Zhang, Michael J. Holtzman, Cameron Sadegh, Towia A. Libermann, Maria K. Lehtinen","doi":"10.1038/s41593-025-01972-9","DOIUrl":null,"url":null,"abstract":"The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT2C receptors (by WAY-161503) triggers sustained Ca2+ signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors lining the brain’s ventricles and shifting their developmental trajectory. Inducing ChP secretion in utero in mice disrupts neural progenitor dynamics, cerebral cortical architecture and offspring behavior. Additionally, illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in the mouse embryo. Our findings reveal a fundamental secretory pathway in the ChP that shapes brain development, highlighting how its disruption can have lasting consequences for brain health.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"4 1","pages":""},"PeriodicalIF":21.2000,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41593-025-01972-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT_2C receptors (by WAY-161503) triggers sustained Ca²⁺ signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors lining the brain’s ventricles and shifting their developmental trajectory. Inducing ChP secretion in utero in mice disrupts neural progenitor dynamics, cerebral cortical architecture and offspring behavior. Additionally, illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in the mouse embryo. Our findings reveal a fundamental secretory pathway in the ChP that shapes brain development, highlighting how its disruption can have lasting consequences for brain health.

Abstract Image

查看原文本刊更多论文

小鼠脑发育过程中脉络丛大汗液分泌影响脑脊液蛋白质组

脉络膜丛（ChP）调节脑脊液（CSF）组成，为大脑发育提供必要的分子线索；然而，胚胎ChP的分泌机制仍不明确。本研究发现胚胎ChP上皮细胞分泌大汗液是雌雄小鼠脑脊液蛋白质组和神经发育的关键调节因子。我们证明了5-羟色胺能5-HT2C受体的激活（通过WAY-161503）触发持续的Ca2+信号，驱动小鼠和人类ChP的大汗液分泌。这种分泌会改变脑脊液蛋白质组，刺激脑室内的神经祖细胞，改变它们的发育轨迹。在小鼠子宫内诱导ChP分泌会破坏神经祖细胞动力学、大脑皮质结构和后代行为。此外，疾病或妊娠期间暴露于麦角酸二乙胺会引起小鼠胚胎中协调的ChP分泌。我们的研究结果揭示了ChP的一个基本分泌途径，它决定了大脑的发育，强调了它的破坏如何对大脑健康产生持久的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature neuroscience 医学-神经科学

CiteScore

38.60

自引率

1.20%

发文量

212

审稿时长

1 months

期刊介绍： Nature Neuroscience, a multidisciplinary journal, publishes papers of the utmost quality and significance across all realms of neuroscience. The editors welcome contributions spanning molecular, cellular, systems, and cognitive neuroscience, along with psychophysics, computational modeling, and nervous system disorders. While no area is off-limits, studies offering fundamental insights into nervous system function receive priority. The journal offers high visibility to both readers and authors, fostering interdisciplinary communication and accessibility to a broad audience. It maintains high standards of copy editing and production, rigorous peer review, rapid publication, and operates independently from academic societies and other vested interests. In addition to primary research, Nature Neuroscience features news and views, reviews, editorials, commentaries, perspectives, book reviews, and correspondence, aiming to serve as the voice of the global neuroscience community.