biostudies-literatureCourtney YSimons FoundationU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)NICHD NIH HHSNIDA NIH HHSNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)NINDS NIH HHSHuman Frontier Science Program (HFSP)NCI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)NIH HHS1446-1459https://www.ebi.ac.uk/biostudies/studies/S-EPMC12229896biostudies-literatureUnknown28(7)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 archiNature neuroscienceChoroid plexus apocrine secretion shapes CSF proteome during mouse brain development.PMC12229896R01NS129823RF1DA048790R01NS088566P30 CA006516RGP0063/2018S10 OD016453R01 NS088566RF1 DA048790P50 HD105351R01 NS129823610670R35 HL145242P30CA006516R35HL145242U54 HD090255Sadegh CDani NLehtinen MKCourtney YChechneva OVZhang YHead JPShipley FBLibermann TAHoltzman MJfalseChoroid plexus apocrine secretion shapes CSF proteome during mouse brain development.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 archi2025-01-01T00:00:00Z2025 Jul2026-07-15T10:52:42.92Z2026-07-03T03:15:53.132ZS-EPMC122298964043705410.1038/s41593-025-01972-9