Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development.
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
Nature Neuroscience July 1, 2025 DOI: 10.1038/s41593-025-01972-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female mice, and human choroid plexus |
| Interventions | WAY-161503 lysergic acid diethylamide |
| Citations | 10 |
| Key findings | Apocrine secretion by embryonic choroid plexus epithelial cells, triggered by serotonergic 5-HT2C receptor activation, regulates the CSF proteome and neurodevelopment, and its disruption can alter brain development and behavior. |
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.